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See full Prescribing & Safety Information.","importantText","HCP Website | DARZALEX® (daratumumab) & DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)\n\nPress Option+1 for screen-reader mode, Option+0 to cancel[Accessibility Screen-Reader Guide, Feedback, and Issue Reporting | New window](https://accessibe.com/blog/knowledgebase/screen-reader-guide)\n\n* [Prescribing Information](#)\n* [PATIENT SITE](https://www.darzalex.com/)\n\n[![DARZALEX® (daratumumab) & DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) logo](/_next/static/media/DarzalexhcpV2_Logo_desktop2x.4e289fa0.svg)](/)\n\n[DARZALEX _FASPRO_® DOSING & ADMINISTRATION GUIDE](/pdfs/dosing-and-administration-guide-faspro.pdf)\n\n[DARZALEX® DOSING & ADMINISTRATION GUIDE](/pdfs/Dosing-and-Administration-Guide.pdf)\n\n[DARZALEX _FASPRO_® monotherapy is the first and only FDA-approved treatment in **high-risk smoldering multiple myeloma**1](/pdfs/aquila.pdf)\n\n[PRODUCT USE](#)\n\n[INDICATIONS AND DOSING](/indications-and-dosing/)\n\n* [Newly Diagnosed](/indications-and-dosing/#newlyDiagnosedDosing)\n * [DVRd](/indications-and-dosing/#newlyDiagnosedDVRdDosing)\n * [DRd](/indications-and-dosing/#newlyDiagnosedDRdDosing)\n * [DVMP](/indications-and-dosing/#newlyDiagnosedDVMPDosing)\n * [DVTd](/indications-and-dosing/#newlyDiagnosedDVTdDosing)\n* [Relapsed or Refractory](/indications-and-dosing/#relapsedRefractoryDosing)\n * [DRd](/indications-and-dosing/#relapsedRefractoryDRdDosing)\n * [DPd](/indications-and-dosing/#relapsedRefractoryDPdDosing)\n * [DKd](/indications-and-dosing/#relapsedRefractoryDKdDosing)\n * [DVd](/indications-and-dosing/#relapsedRefractoryDVdDosing)\n * [Monotherapy](/indications-and-dosing/#relapsedRefractoryMonotherapyDosing)\n\n* [NCCN RECOMMENDATIONS](/nccn-recommendations/)\n* [ADMINISTRATION](/administration/)\n\n[FRONTLINE DVRd](#)\n\n* [PATIENT PROFILE](/frontline-dvrd/#PatientProfile)\n* [PERSEUS STUDY](/frontline-dvrd/#PerseusStudy)\n* [PROVEN EFFICACY](/frontline-dvrd/#ProvenEfficacy)\n* [DEMONSTRATED SAFETY](/frontline-dvrd/#DemonstratedSafety)\n\n[FRONTLINE DRd](#)\n\n* [PATIENT TYPES](/frontline-drd/#PatientTypes)\n* [PROVEN EFFICACY](/frontline-drd/#ProvenEfficacy)\n* [DEMONSTRATED SAFETY](/frontline-drd/#DemonstratedSafety)\n* [HIGH-RISK SUBGROUP](/frontline-drd/#High-RiskSubgroup)\n* [FRAILTY SUBGROUP](/frontline-drd/#FrailtySubgroup)\n* [AGE SUBGROUP](/frontline-drd/#AgeSubgroup)\n\n[CONTINUING DRd TREATMENT](#)\n\n* [MAINTAINING TREATMENT BENEFITS](/continuing-drd-treatment/#maintainingTreatmentBenefits)\n* [TIME TO DEEPEST RESPONSE](/continuing-drd-treatment/#timeDeepestResponse)\n* [SAFETY OVER TIME](/continuing-drd-treatment/#safetyOverTime)\n* [ADVANCING PATIENT CARE](/continuing-drd-treatment/#advancePatientCare)\n\n[RESOURCES](#)\n\n* [PRACTICE SUPPORT](/multiple-myeloma-resources/#practiceSupport)\n* [PATIENT SUPPORT](/multiple-myeloma-resources/#patientSupport)\n* [MECHANISM OF ACTION](/multiple-myeloma-resources/#mechanismOfAction)\n* [GET IN TOUCH](/multiple-myeloma-resources/#getintouch)\n* [Q&A](/multiple-myeloma-resources/#faqTab)\n\n[FOR APPs & NURSES](/for-APPs-and-nurses/)\n\n* [PRESCRIBING INFORMATION](#)\n \n * [DARZALEX _FASPRO_® Prescribing Information](https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf)\n * [DARZALEX _FASPRO_® la información de prescripción](/#)\n * [DARZALEX® Prescribing Information](https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf)\n \n* [Important Safety Information](#)\n \n * [DARZALEX _FASPRO_® Important Safety Information](/#)\n * [DARZALEX® Important Safety Information](/#)\n \n* [Contact Us](#)\n \n * [1-833-565-9631](tel:1-800-JANSSEN)\n * [Email Medical Information Center](https://www.askjanssenmedicalinformation.com/step1-contact-information)\n * [SEARCH J&J MEDICAL CONNECT](https://www.janssenmd.com/)\n * [CONTACT US](https://www.jnjmedicalconnect.com/contact-us)\n \n* [Dosing & Administration Guide](#)\n \n * [DARZALEX _FASPRO_® Dosing & Administration Guide](/pdfs/dosing-and-administration-guide-faspro.pdf)\n * [DARZALEX® Dosing & Administration Guide](/pdfs/Dosing-and-Administration-Guide.pdf)\n \n* [PATIENT SITE](https://www.darzalex.com/)\n* [MM Portfolio](https://www.immunotherapy4myeloma.com/)\n* This site is intended for \n US healthcare professionals.\n\n[\n\nChoose DARZALEX _FASPRO_® to treat newly diagnosed patients with multiple myeloma, regardless of transplant status\n\n\n\n\n\n](/frontline-dvrd#PatientProfile)\n\nPrevious\n\n![Image of Dr Fanning, MD](/images/carousel-two_Fanning-mb.png)\n\nHEAR FROM MULTIPLE MYELOMA EXPERTS\n----------------------------------\n\nWatch multiple myeloma experts provide their perspectives on treating newly diagnosed, transplant-ineligible multiple myeloma\n\n[View videos](/#kol-videos)\n\n![N/A](/images/home_carousel_three_mobile.png)\n\nPATIENT TYPES\n\nFor newly diagnosed multiple myeloma3,4\n\n### Frontline \nREGIMENS \nfor a range \nof patients\n\nHypothetical patient cases created for illustrative purposes.\n\n[Examine patient cases](/frontline-drd/)\n\n![patient-type picture of Janice](/_next/static/media/patient-persona-janice.5e5212f4.png)\n\nTransplant-ineligible patient with moderately active lifestyle\n\n![patient-type picture of Luis](/_next/static/media/patient-persona-luis.22bfd531.png)\n\nTransplant-ineligible patient \nwith high-risk cytogenetics‡\n\n![patient-type picture of Samuel](/_next/static/media/patient-persona-samuel.7005c43b.png)\n\nElderly transplant-ineligible \npatient with comorbidities\n\n![patient-type picture of Helen](/_next/static/media/patient-persona-helen.b90dd2e5.png)\n\nYounger transplant-ineligible patient\n\n![Image of healthcare professionals rolling out Darzalex efficacy results](/images/carousel-one_PERSEUS_mobile.png)\n\n![Perseus Logo](/images/splashpage/perseusLogo.svg)\n\nIn the treatment of newly diagnosed multiple myeloma1:\n\nGive transplant-eligible patients a better chance at experiencing improved outcomes with DARZALEX _faspro_® + VRd vs VRd ALONE1\n===============================================================================================================================\n\n**After 47.5 months, 60% reduction in the risk of progression or death with DVRd vs VRd alone in the PERSEUS trial (HR=0.40; 95% CI: 0.29-0.57; _P_<0.0001; mPFS not reached in either arm).1,2\\***\n\n[See the data](/frontline-dvrd/#progression)\n\n![Image of Dr Fanning, MD](/images/carousel-two_Fanning-mb.png)\n\nHEAR FROM MULTIPLE MYELOMA EXPERTS\n----------------------------------\n\nWatch multiple myeloma experts provide their perspectives on treating newly diagnosed, transplant-ineligible multiple myeloma\n\n[View videos](/#kol-videos)\n\n![N/A](/images/home_carousel_three_mobile.png)\n\nPATIENT TYPES\n\nFor newly diagnosed multiple myeloma3,4\n\n### Frontline \nREGIMENS \nfor a range \nof patients\n\nHypothetical patient cases created for illustrative purposes.\n\n[Examine patient cases](/frontline-drd/)\n\n![patient-type picture of Janice](/_next/static/media/patient-persona-janice.5e5212f4.png)\n\nTransplant-ineligible patient with moderately active lifestyle\n\n![patient-type picture of Luis](/_next/static/media/patient-persona-luis.22bfd531.png)\n\nTransplant-ineligible patient \nwith high-risk cytogenetics‡\n\n![patient-type picture of Samuel](/_next/static/media/patient-persona-samuel.7005c43b.png)\n\nElderly transplant-ineligible \npatient with comorbidities\n\n![patient-type picture of Helen](/_next/static/media/patient-persona-helen.b90dd2e5.png)\n\nYounger transplant-ineligible patient\n\n![Image of healthcare professionals rolling out Darzalex efficacy results](/images/carousel-one_PERSEUS_mobile.png)\n\n![Perseus Logo](/images/splashpage/perseusLogo.svg)\n\nIn the treatment of newly diagnosed multiple myeloma1:\n\nGive transplant-eligible patients a better chance at experiencing improved outcomes with DARZALEX _faspro_® + VRd vs VRd ALONE1\n===============================================================================================================================\n\n**After 47.5 months, 60% reduction in the risk of progression or death with DVRd vs VRd alone in the PERSEUS trial (HR=0.40; 95% CI: 0.29-0.57; _P_<0.0001; mPFS not reached in either arm).1,2\\***\n\n[See the data](/frontline-dvrd/#progression)\n\n![Image of Dr Fanning, MD](/images/carousel-two_Fanning-mb.png)\n\nHEAR FROM MULTIPLE MYELOMA EXPERTS\n----------------------------------\n\nWatch multiple myeloma experts provide their perspectives on treating newly diagnosed, transplant-ineligible multiple myeloma\n\n[View videos](/#kol-videos)\n\n![N/A](/images/home_carousel_three_mobile.png)\n\nPATIENT TYPES\n\nFor newly diagnosed multiple myeloma3,4\n\n### Frontline \nREGIMENS \nfor a range \nof patients\n\nHypothetical patient cases created for illustrative purposes.\n\n[Examine patient cases](/frontline-drd/)\n\n![patient-type picture of Janice](/_next/static/media/patient-persona-janice.5e5212f4.png)\n\nTransplant-ineligible patient with moderately active lifestyle\n\n![patient-type picture of Luis](/_next/static/media/patient-persona-luis.22bfd531.png)\n\nTransplant-ineligible patient \nwith high-risk cytogenetics‡\n\n![patient-type picture of Samuel](/_next/static/media/patient-persona-samuel.7005c43b.png)\n\nElderly transplant-ineligible \npatient with comorbidities\n\n![patient-type picture of Helen](/_next/static/media/patient-persona-helen.b90dd2e5.png)\n\nYounger transplant-ineligible patient\n\nNext\n\n* 1\n* 2\n* 3\n\n**After 47.5 months, 60% reduction in the risk of progression or death with DVRd vs VRd alone in the PERSEUS trial (HR=0.40; 95% CI: 0.29-0.57;_P_<0.0001; mPFS not reached in either arm)**.1,2\\*\n\n![Continuous treatment icon](/_next/static/media/icon-continuous-treatment.e5f0491d.svg)\n\nKeep patients on a proven path with frontline DARZALEX® + Rd for newly diagnosed, transplant-ineligible multiple myeloma3\n\n[Explore continuing treatment](/continuing-drd-treatment/)\n\n![Checklist icon](/_next/static/media/icon-check-mark.0b3384e6.svg)\n\nNCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommendations for regimens containing daratumumab (DARZALEX®)\n\n[Discover NCCN recommendations](/nccn-recommendations/)\n\n![Syringe icon](/_next/static/media/icon-faspro.d7adc7e4.svg)\n\nAdministration options include ~3 to 5 minute subcutaneous DARZALEX _FASPRO_® and intravenous DARZALEX®1,3†\n\n[Learn about sub-Q administration](/administration/)\n\n\\* Median follow-up was 47.5 months in the DVRd and VRd group (range: 0.0-54.4 months).2\n\n†DARZALEX _FASPRO_® is administered by subcutaneous injection over approximately 3 to 5 minutes. In contrast, DARZALEX® is administered by intravenous infusion over approximately 7, 4, and 3 hours for first, second, and subsequent infusions, respectively.1,3 [View IV administration](/administration/#darzalexAdministration)\n\n‡Cytogenetic risk was based on fluorescence in situ hybridization (FISH) or karyotype analysis. High-risk cytogenetics were defined as having at least one of the following abnormalities: t\\[4;14\\], t\\[14;16\\], del\\[17p\\], t\\[14;20\\], gain\\[1q21\\], amp\\[1q21\\].4\n\nAdvancing frontline knowledge: KOL expert series\n------------------------------------------------\n\nVideo Player is loading.\n\nPlay Video\n\nPlay\n\nMute\n\nCurrent Time 0:00\n\n/\n\nDuration 30:40\n\nLoaded: 0.54%\n\n00:00\n\nStream Type LIVE\n\nSeek to live, currently behind liveLIVE\n\nRemaining Time \\-30:40\n\nShare\n\n1x\n\nPlayback Rate\n\nChapters\n\n* Chapters\n\nDescriptions\n\n* descriptions off, selected\n\nCaptions\n\n* captions settings, opens captions settings dialog\n* captions off, selected\n\nAudio Track\n\n* en (Main), selected\n\nPicture-in-Picture\n\nQuality Levels\n\n* 720p720pHD\n* 576p576p\n* 432p432p\n* 288p288p\n* AutoA, selected\n\nFullscreen\n\nThis is a modal window.\n\nBeginning of dialog window. Escape will cancel and close the window.\n\nTextColorWhiteBlackRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-Transparent\n\nBackgroundColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentTransparent\n\nWindowColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyTransparentSemi-TransparentOpaque\n\nFont Size50%75%100%125%150%175%200%300%400%\n\nText Edge StyleNoneRaisedDepressedUniformDropshadow\n\nFont FamilyProportional Sans-SerifMonospace Sans-SerifProportional SerifMonospace SerifCasualScriptSmall Caps\n\nReset restore all settings to the default valuesDone\n\nClose Modal Dialog\n\nEnd of dialog window.\n\nClose Modal Dialog\n\nThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.\n\nClose Modal Dialog\n\nThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.\n\nContinuous frontline treatment with DARZALEX® + Rd and patient outcomes\n\nDr. Suzanne Reim Fanning, Associate Professor at USC School of Medicine Greenville, discusses what the research says about the importance of continuing frontline treatment with DARZALEX® until disease progression or unacceptable toxicity, and how doing so shapes outcomes for patients with multiple myeloma.\n\nView video transcript\n---------------------\n\n00:00:14 —\\> 00:00:19\n\nThis is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.\n\n00:00:20 —\\> 00:00:28\n\nFaculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.\n\n00:00:31 —\\> 00:00:37\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:00:38 —\\> 00:00:50\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.\n\n00:00:51 —\\> 00:00:53\n\n**Select Important Safety Information.**\n\n00:00:54 —\\> 00:01:05\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.\n\n00:01:06 —\\> 00:01:22\n\n**Warnings and Precautions: Infusion-Related Reactions**\n\nDARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.\n\n00:01:22 —\\> 00:01:49\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:01:50 —\\> 00:01:53\n\nAdditional Important Safety Information will be reviewed later in this video.\n\n00:01:55 —\\> 00:01:58\n\nPlease see full Prescribing Information available on this website.\n\n00:02:00 —\\> 00:02:09\n\nDo you know how important the duration of frontline DRd treatment is for managing patients with newly diagnosed, transplant-ineligible multiple myeloma?\n\n00:02:10 —\\> 00:02:13\n\nHello, I’m Dr. Fanning.\n\n00:02:13 —\\> 00:02:28\n\nJoin me as we discover why continuous treatment with frontline DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, is a proven path for newly diagnosed patients with transplant-ineligible multiple myeloma.\n\n00:02:29 —\\> 00:03:04\n\nOur first topic will cover the importance of frontline treatment in multiple myeloma and why it is an ideal opportunity for achieving deep response. Next, we’ll shift to topics on DARZALEX® treatment, starting with the results of the MAIA trial that studied continuous treatment with frontline DRd versus Rd, or lenalidomide and dexamethasone alone. Once we’ve covered that, we’ll take a closer look at a post hoc subset analysis of DRd and Rd treatment duration and patient outcomes.\n\n00:03:05 —\\> 00:03:22\n\nThis subset analysis covers patients treated for at least 18 months and we’ll get a better understanding about maintaining treatment benefits with frontline DRd, looking specifically at time to deepest response and safety over time.\n\n00:03:26 —\\> 00:04:08\n\nResearch demonstrates that the depth of response patients achieve worsens with later lines of therapy. For example, in this retrospective study conducted in 7 European countries, 435 physicians reviewed 4,997 patient charts to map the course of patients with multiple myeloma and to investigate the factors that influence treatment decisions at different stages of the treatment journey. Depth of response, as assessed by the treating physician, was evaluated at each subsequent line of therapy. Profiles of patients with multiple myeloma during the last 12 months were similar across study sites.\n\n00:04:09 —\\> 00:04:57\n\nThe likelihood of achieving deep response was found to decrease with subsequent lines of treatment for patients with multiple myeloma. The proportion of patients achieving a complete response decreased from 32% at frontline to 4% at fourth line and 2% at fifth line. Similarly, 74% of patients achieved at least a very good partial response with the frontline treatment, compared with only 11% with the fifth line or later. These real-world data provide an insight into patient outcomes and treatment decisions being made in clinical practice. As you can see, frontline treatment is the most appropriate time to aim for deep response compared with later lines of treatment.\n\n00:05:01 —\\> 00:05:06\n\nBefore we look at the data, let’s get a good understanding of the trial design.\n\n00:05:07 —\\> 00:05:38\n\nMAIA was a large, randomized, open-label, multicenter, active-controlled, phase 3 trial that compared DRd vs Rd in a wide range of adult patients with newly diagnosed, transplant-ineligible multiple myeloma. Three hundred sixty-eight patients were randomized to the DRd arm, and three hundred sixty-nine patients were randomized to the Rd arm. Treatment was continued until disease progression or unacceptable toxicity.\n\n00:05:39 —\\> 00:05:42\n\nThe primary endpoint was progression-free survival.\n\n00:05:42 —\\> 00:06:00\n\nKey secondary endpoints included rates of complete response or better, rates of very good partial response or better, rates of minimal residual disease-negativity, overall response rate, overall survival, duration of response, and safety.\n\n00:06:02 —\\> 00:06:41\n\nBaseline demographics and disease characteristics were similar between the 2 treatment groups. In the DRd arm, the median age of patients was 73 years. Thirty-four percent had an Eastern Cooperative Oncology Group Performance Status, or ECOG PS, of 0, 50% had an ECOG PS of 1, and 17% had an ECOG PS of 2 or more. Twenty-seven percent had International Staging System, or ISS, Stage I, 43% percent had ISS Stage II, and 29% percent had ISS Stage III disease.\n\n00:06:42 —\\> 00:06:58\n\nNow that we have looked at how the MAIA trial was designed, let’s review the primary results of the trial, which showed that frontline DRd significantly reduced the risk of disease progression or death in patients after 28 months of follow-up.\n\n00:07:01 —\\> 00:07:24\n\nMedian PFS was not reached with DRd vs 31.9 months with Rd alone. The hazard ratio was 0.56, with a 95% confidence interval that ranged from 0.43 to 0.73. These results were significant, with a P-value of less than 0.0001.\n\n00:07:26 —\\> 00:07:34\n\nThis translates to a 44% risk reduction for disease progression or death with DRd vs Rd alone.\n\n00:07:35 —\\> 00:07:54\n\nThe median duration of study treatment was 25.3 months (range 0.1 to 40.44 months) in the DRd group and 21.3 months (range 0.03 to 40.64 months) in the Rd group.\n\n00:07:54 —\\> 00:07:57\n\nNow let’s look at long-term progression-free survival.\n\n00:07:59 —\\> 00:08:07\n\nAfter a median follow-up of 64 months, patients were progression-free longer with DRd vs Rd alone.\n\n00:08:08 —\\> 00:08:28\n\nThe median PFS was 61.9 months with a 95% confidence interval that ranged from 54.8 to not estimable with DRd, versus 34.4 months with a 95% confidence interval that ranged from 29.6 to 39.2 with Rd alone.\n\n00:08:30 —\\> 00:08:39\n\nThe hazard ratio was 0.55 with a 95% confidence interval that ranged from 0.45 to 0.67.\n\n00:08:40—\\> 00:08:48\n\nThis translates to a 45% risk reduction for disease progression or death with DRd vs Rd alone.\n\n00:08:49 —\\> 00:08:55\n\nNow, let’s look at the additional efficacy results of overall response rate from the MAIA trial.\n\n00:08:56 —\\> 00:09:04\n\nAs you can see, a 93% overall response rate was achieved with DRd after a median follow-up of 28 months.\n\n00:09:05 —\\> 00:09:19\n\nThe median time to response was 1.05 months with DRd with a range from 0.2 to 12.1 months. With Rd the range was from 0.3 to 15.3 months.\n\n00:09:20 —\\> 00:09:33\n\nAnd the median duration of response was not reached with DRd vs 34.7 months with Rd alone, with a 95% confidence interval that ranged from 30.8 to not estimable.\n\n00:09:35 —\\> 00:09:43\n\nIt is important to note that approximately 50% of patients in the MAIA trial achieved complete response or better with frontline DRd.\n\n00:09:43 —\\> 00:09:46\n\nThat’s nearly 2 times greater than Rd alone.\n\n00:09:47 —\\> 00:10:10\n\nIn addition to efficacy, the safety of adding DARZALEX® to lenalidomide and dexamethasone was also evaluated. Adverse reactions you are seeing reflect exposure to DARZALEX® plus Rd for a median treatment duration of 25.3 months and Rd for 21.3 months, as reported in the primary analysis.\n\n00:10:11 —\\> 00:10:23\n\nThe most frequently reported adverse reactions were diarrhea, upper respiratory tract infection, infusion-related reactions, constipation, peripheral edema, and fatigue.\n\n00:10:24 —\\> 00:10:48\n\nInfusion-related reactions with DRd occurred in 41% of patients; 2% were Grade 3 and <1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion. Most infusion-related reactions occurred during the first infusion.\n\n00:10:49 —\\> 00:11:00\n\nSerious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.\n\n00:11:01 —\\> 00:11:13\n\nThe most frequently reported hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.\n\n00:11:13 —\\> 00:11:25\n\nHematologic abnormalities were more prevalent in the DARZALEX® plus Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® plus Rd arm.\n\n00:11:26 —\\> 00:12:03\n\nDARZALEX® can cause severe and/or serious infusion-related reactions, including anaphylactic reactions. In clinical trials (monotherapy and combination: N=2,066), infusion-related reactions, occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3 or 4 infusion-related reaction at Week 2 or subsequent infusions.\n\n00:12:04 —\\> 00:12:25\n\nBefore we move to our next topic on treatment duration and patient outcomes, let’s consider the case of this hypothetical patient. This is Mindy. Imagine she’s a patient in your practice being treated with frontline therapy. She could be a good candidate for the benefits of maintaining treatment on DRd. Let’s consider her case.\n\n00:12:26 —\\> 00:12:43\n\nMindy’s multiple myeloma was diagnosed 12 months ago following lower back and neck pain and was put on frontline DRd. She was ISS disease stage II and her ECOG PS score was 1. She was also on treatment for early-stage Parkinson’s.\n\n00:12:44 —\\> 00:12:49\n\nGiven her condition and disease presentation, Mindy was considered ineligible for transplant.\n\n00:12:50 —\\> 00:12:53\n\nShe is currently continuing her treatment with DRd.\n\n00:12:54 —\\> 00:13:04\n\nWhen you start a patient like Mindy on frontline DRd, are you keeping them on treatment until disease progression or unacceptable toxicity, as was done for patients in the MAIA trial?\n\n00:13:09 —\\> 00:13:16\n\nNow, let’s shift our attention to a post hoc subset analysis of treatment duration and patient outcomes.\n\n00:13:17 —\\> 00:13:25\n\nIt’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.\n\n00:13:26 —\\> 00:13:32\n\nAdditionally, no conclusions should be drawn. These data should be understood in the context of the methodology.\n\n00:13:34 —\\> 00:13:59\n\nLet’s first look at the methodology of this post hoc subset analysis. To explore the impact of treatment duration on long-term clinical outcomes, a post hoc analysis was conducted based on DRd treatment duration (<18 vs 18 months), excluding patients who discontinued therapy due to disease progression during the first 18 months.\n\n00:14:00 —\\> 00:14:28\n\nThe DRd arm included 283 patients who were treated for at least 18 months, out of 368 patients of the primary intent-to-treat (ITT) analysis of the MAIA trial. The Rd arm included 204 patients, who were treated for at least 18 months, out of 369 patients of the primary ITT analysis of the MAIA trial.\n\n00:14:30 —\\> 00:14:43\n\nResponse data presented are cumulative deepest response rates achieved by 6, 9, and 18 months for patients who continued all trial treatment for at least 18 months.\n\n00:14:44 —\\> 00:14:53\n\nAs you can see, more patients achieved complete response or better by 18 months vs 6 months of DARZALEX® + Rd treatment.\n\n00:14:54—\\> 00:15:02\n\nRates of complete response or better increased over 6, 9, and 18 months of continuous frontline DRd.\n\n00:15:03 —\\> 00:15:14\n\nApproximately 50% of patients achieved complete response or better by 18 months of DRd treatment compared with approximately 9% by 6 months of treatment.\n\n00:15:14 —\\> 00:15:25\n\nPost hoc subset analysis of the Rd treatment group also showed that more patients achieved complete response or better by 18 months vs 6 months.\n\n00:15:26 —\\> 00:15:33\n\nRates of complete response or better increased over 6, 9, and 18 months of continuous frontline Rd.\n\n00:15:34 —\\> 00:15:45\n\nApproximately 30% of patients achieved complete response or better by 18 months of Rd treatment compared with approximately 4% by 6 months of treatment.\n\n00:15:47 —\\> 00:16:08\n\nYou can see from the results presented that more patients achieved a complete response or better with DRd by 18 months vs Rd alone. Forty-nine point eight percent of the patients receiving DRd achieved complete response or better by 18 months vs 30.4% receiving Rd.\n\n00:16:09 —\\> 00:16:21\n\nThis post hoc subset analysis shows the increase in complete response rates over 6, 9, and 18 months with continuous frontline DRd.\n\n00:16:22 —\\> 00:16:30\n\nGetting back to the hypothetical patient, Mindy, the duration of treatment may be an important consideration for her multiple myeloma treatment.\n\n00:16:31 —\\> 00:16:42\n\nIf patients like Mindy do not stay on their treatment beyond 6 months, or even 9 months of therapy, they may not experience the benefits achieved by 18 months of therapy.\n\n00:16:47 —\\> 00:16:57\n\nLet’s take a closer look at another post hoc subset analysis that evaluated frequently reported adverse events over time for patients who continued their treatment.\n\n00:16:58 —\\> 00:17:05\n\nIt’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.\n\n00:17:06 —\\> 00:17:18\n\nAdditionally, no conclusions should be drawn. In the following analysis, treatment-emergent adverse events are presented as observed and should be understood in context with the specific methodology.\n\n00:17:20 —\\> 00:17:43\n\nFirst, let’s review some of the methodology for this analysis. Most frequently reported treatment-emergent adverse events, or TEAEs, that met the threshold of cumulative any-grade greater than or equal to 30%, or Grade 3 or 4 greater than or equal to 10%, are presented here.\n\n00:17:44 —\\> 00:17:53\n\nCombined TEAE rates are the sum of the percentages of the most frequently reported events at each cycle period.\n\n00:17:54 —\\> 00:18:06\n\nPercentages represent the number of patients with one or more TEAEs by treatment cycle divided by the total number of patients treated within the treatment window.\n\n00:18:07 —\\> 00:18:31\n\nOnly TEAEs with an onset date falling within the cycle intervals were calculated. Each patient was calculated once per preferred term for each cycle interval. The same patient could be calculated in multiple cycle intervals and for multiple preferred terms. TEAEs may not have resolved by the next cycle.\n\n00:18:32 —\\> 00:18:48\n\nDecrease in adverse event rates, or AE rates, over time from treatment initiation was observed for most AEs in both treatment arms. Cataract tended to increase over time in both treatment arms.\n\n00:18:49 —\\> 00:19:02\n\nThirteen percent of intent-to-treat patients discontinued treatment due to a TEAE with DRd vs 22% of the patients with Rd alone.\n\n00:19:03 —\\> 00:19:13\n\nIn patients who continued treatment, most AE rates decreased over time from treatment initiation to ~30 months for DRd.\n\n00:19:14 —\\> 00:19:24\n\nIn the Rd arm, patients who continued treatment also experienced decreased AE rates over time from treatment initiation to approximately 30 months.\n\n00:19:25 —\\> 00:19:33\n\nYou can now see the observed overall AE rates for DRd, which are combined rates of most frequent AEs per treatment cycle.\n\n00:19:34 —\\> 00:19:49\n\nWhen you examine the chart, you can see that in patients who continued treatment, combined rates of frequently reported TEAEs decreased over time from treatment initiation to approximately 30 months for DRd.\n\n00:19:49 —\\> 00:20:01\n\nIn patients who continued treatment, combined rates of frequently reported TEAEs decreased over time from treatment initiation to approximately 30 months for Rd.\n\n00:20:02 —\\> 00:20:21\n\nAs an oncologist, you have the opportunity at the time of treatment initiation to set duration of therapy expectations with your patient. This important conversation can help ensure that both you and your patients like Mindy are on the same page in terms of what to expect throughout the course of therapy.\n\n00:20:22 —\\> 00:20:31\n\nBefore I conclude this video on Advancing Frontline Knowledge and present the summary, I would like to share the Important Safety Information about DARZALEX®.\n\n00:20:33 —\\> 00:20:48\n\n**IMPORTANT SAFETY INFORMATION**\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity. For example, anaphylactic reactions to daratumumab or any of the components of the formulation.\n\n00:20:49 —\\> 00:22:15\n\n**WARNINGS AND PRECAUTIONS**\n\n**Infusion-Related Reactions**\n\nDARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3 or 4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.\n\n00:22:16 —\\> 00:23:21\n\nWhen DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.\n\n00:23:22 —\\> 00:23:52\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:23:52 —\\> 00:24:17\n\nTo reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.\n\n00:24:18 —\\> 00:24:39\n\nOcular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.\n\n00:24:41 —\\> 00:24:52\n\n**Interference With Serological Testing**\n\nDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test).\n\n00:24:53 —\\> 00:25:25\n\nDaratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.\n\n00:25:26 —\\> 00:25:51\n\n**Neutropenia and Thrombocytopenia**\n\nDARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.\n\n00:25:52 —\\> 00:26:22\n\n**Interference With Determination of Complete Response**\n\nDaratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.\n\n00:26:23 —\\> 00:26:49\n\n**Embryo-Fetal Toxicity**\n\nBased on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.\n\n00:26:49 —\\> 00:27:09\n\nThe combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.\n\n00:27:10 —\\> 00:27:47\n\n**ADVERSE REACTIONS**\n\nThe most frequently reported adverse reactions (incidence ≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.\n\n00:27:47 —\\> 00:27:55\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:27:56 —\\> 00:28:09\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.\n\n00:28:10 —\\> 00:28:18\n\nIn combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant.\n\n00:28:19 —\\> 00:28:27\n\nIn combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant.\n\n00:28:27 —\\> 00:28:34\n\nIn combination with bortezomib and dexamethasone in patients who have received at least one prior therapy.\n\n00:28:34 —\\> 00:28:44\n\nIn combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.\n\n00:28:44 —\\> 00:28:54\n\nIn combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.\n\n00:28:54 —\\> 00:29:08\n\nAs monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.\n\n00:29:08 —\\> 00:29:13\n\nPlease see full Prescribing Information available on this website.\n\n00:29:17 —\\> 00:29:33\n\nIn summary, in the treatment of newly diagnosed, transplant-ineligible multiple myeloma, we have seen the benefit of progression-free survival with frontline DRd vs Rd therapy after 28 months and 64 months of follow up.\n\n00:29:34 —\\> 00:29:52\n\nWe also looked at a post hoc subset analysis of patients who stayed on their treatment for 18 months. We saw that more patients achieved complete response or better at 18 months with DRd and Rd vs 6 months of DRd and Rd.\n\n00:29:53 —\\> 00:30:03\n\nFor the best chance of achieving progression-free survival seen in the MAIA trial, patients should be treated with DRd until disease progression or unacceptable toxicity.\n\n00:30:04 —\\> 00:30:18\n\nBased on this body of evidence from the MAIA trial supporting use of continuous DRd treatment, are you ready to keep your newly diagnosed transplant-ineligible patients on a proven path with DARZALEX® + Rd?\n\nVideo Player is loading.\n\nPlay Video\n\nPlay\n\nMute\n\nCurrent Time 0:00\n\n/\n\nDuration 23:15\n\nLoaded: 0.70%\n\n00:00\n\nStream Type LIVE\n\nSeek to live, currently behind liveLIVE\n\nRemaining Time \\-23:15\n\nShare\n\n1x\n\nPlayback Rate\n\nChapters\n\n* Chapters\n\nDescriptions\n\n* descriptions off, selected\n\nCaptions\n\n* captions settings, opens captions settings dialog\n* captions off, selected\n\nAudio Track\n\n* en (Main), selected\n\nPicture-in-Picture\n\nQuality Levels\n\n* 1080p1080pHD\n* 900p900pHD\n* 576p576p\n* 360p360p\n* 216p216p\n* AutoA, selected\n\nFullscreen\n\nThis is a modal window.\n\nBeginning of dialog window. Escape will cancel and close the window.\n\nTextColorWhiteBlackRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-Transparent\n\nBackgroundColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentTransparent\n\nWindowColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyTransparentSemi-TransparentOpaque\n\nFont Size50%75%100%125%150%175%200%300%400%\n\nText Edge StyleNoneRaisedDepressedUniformDropshadow\n\nFont FamilyProportional Sans-SerifMonospace Sans-SerifProportional SerifMonospace SerifCasualScriptSmall Caps\n\nReset restore all settings to the default valuesDone\n\nClose Modal Dialog\n\nEnd of dialog window.\n\nClose Modal Dialog\n\nThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.\n\nClose Modal Dialog\n\nThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.\n\nPatient considerations when determining frontline treatment\n\nDr. Kenneth Shain, Director of the Myeloma Working Group at Moffitt Cancer Center (Tampa, Florida), discusses a typical patient seen in his practice and how he reviews safety and efficacy data along with NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) when choosing a frontline treatment option.\n\nView video transcript\n---------------------\n\n00:00:14 —\\> 00:00:21\n\nThis is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.\n\n00:00:21 —\\> 00:00:30\n\nFaculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.\n\n00:00:31 —\\> 00:00:38\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:00:38 —\\> 00:00:53\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.\n\n00:00:53 —\\> 00:00:55\n\n**Select Important Safety Information**.\n\n00:00:55 —\\> 00:01:09\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.\n\n00:01:10 —\\> 00:01:25\n\n**Warnings and Precautions: Infusion-Related Reactions**\n\nDARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.\n\n00:01:26 —\\> 00:01:57\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:01:58 —\\> 00:02:01\n\nAdditional Important Safety Information will be reviewed later in this video.\n\n00:02:02 —\\> 00:02:14\n\n**DR. SHAIN**: I see a broad range of patients with newly diagnosed, transplant-ineligible multiple myeloma in my practice, and I usually spend time taking into account their individual characteristics.\n\n00:02:14 —\\> 00:02:26\n\n**DR. SHAIN**: The question I face is one that you may also encounter—whether the benefits and safety profile of a particular frontline therapy line up with the needs and the medical situation of the patient.\n\n00:02:27 —\\> 00:02:37\n\n**DR. SHAIN**: Hello, I am Dr. Kenneth Shain. Join me, as I discuss a frontline treatment option for newly diagnosed, transplant-ineligible multiple myeloma patients...\n\n00:02:37 —\\> 00:02:47\n\n**DR. SHAIN**:...based on evidence of efficacy and safety results from the MAIA study at 30 months, as well as the follow-up data at approximately 5 years.\n\n00:02:48 —\\> 00:03:11\n\n**DR. SHAIN**: Here is Janice, a patient I typically treat in my practice. She is a 73-year-old retired schoolteacher and a grandmother who was recently diagnosed with multiple myeloma and is not eligible for autologous stem cell transplant. She presented with International Staging System, or ISS, stage II as well as Eastern Cooperative Oncology Group, or ECOG, performance status of 1.\n\n00:03:11 —\\> 00:03:16\n\nWhen considering a frontline treatment option, we need to be thoughtful of her patient characteristics.\n\n00:03:17 —\\> 00:03:29\n\n**DR. SHAIN**: DARZALEX® plus lenalidomide and dexamethasone offers the opportunity for advancing frontline treatment with your patients who are newly diagnosed and transplant-ineligible.\n\n00:03:30 —\\> 00:03:39\n\n**DR. SHAIN**: The MAIA study was a large, randomized, open-label, multicenter, active-controlled phase 3 study of DRd, vs Rd alone.\n\n00:03:40 —\\> 00:03:48\n\n**DR. SHAIN**: The study included 737 adult patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant.\n\n00:03:49 —\\> 00:04:26\n\nPatients were randomized, 1 to 1, to either receive DARZALEX® 16 mg/kg by intravenous infusion, weekly for Cycles 1 and 2, every 2 weeks for Cycles 3 through 6, and every 4 weeks for Cycles 7 and beyond, in combination with oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone at 40 mg weekly in the DRd arm; or oral lenalidomide at 25 mg daily, Days 1 through 21, and oral dexamethasone 40 mg weekly, as the active control group: the Rd arm.\n\n00:04:26 —\\> 00:04:32\n\nPatients in both treatment arms continued until disease progression or unacceptable toxicity.\n\n00:04:33 —\\> 00:04:36\n\n**DR. SHAIN**: The primary endpoint of the study was progression-free survival.\n\n00:04:37 —\\> 00:04:50\n\nKey secondary endpoints included a percentage of patients with complete response rate, very good partial response rate, minimal residual disease-negativity rate, overall response rate, overall survival, and of course, safety.\n\n00:04:51 —\\> 00:04:54\n\n**DR. SHAIN**: Let’s first look at the demographics of the patients included in the study.\n\n00:04:54 —\\> 00:05:04\n\nThe median age was 73 years, with a range of 45 to 90 years in the DRd arm, with 44% of the patients aged 75 years or more.\n\n00:05:04 —\\> 00:05:17\n\nIn the DRd arm, thirty-four patients, or 35%, had an ECOG performance score of 0, 48% had an ECOG performance score of 1, and 17% had an ECOG performance score of 2 or more.\n\n00:05:17 —\\> 00:05:27\n\nTwenty-seven percent of patients had an ISS stage I, 44% had an ISS stage II, and 29% had an ISS stage III disease.\n\n00:05:27 —\\> 00:05:33\n\n**DR. SHAIN**: I am always inclined to look at the data when making a treatment decision for patients who have distinctive needs.\n\n00:05:34 —\\> 00:05:39\n\nSo, for a patient like Janice let’s see how DRd fits into a frontline treatment.\n\n00:05:40 —\\> 00:05:46\n\n**DR. SHAIN**: The MAIA study reported that DRd demonstrated superior efficacy vs Rd alone.\n\n00:05:46 —\\> 00:05:52\n\nLet’s first discuss the primary analysis data and then we can get into the approximately 5-year follow-up results.\n\n00:05:53 —\\> 00:06:00\n\nAs mentioned, progression-free survival was the primary endpoint for the MAIA study. Let’s take a look at the results of this key data point.\n\n00:06:01 —\\> 00:06:10\n\n**DR. SHAIN**: The median progression-free survival for DRd was not reached in the MAIA study, while the median progression-free survival for Rd was 31.9 months.\n\n00:06:11 —\\> 00:06:26\n\nThe median follow-up was about 30 months. The data reported a hazard ratio of 0.56; with a 95% confidence interval of 0.43 to 0.73, and a p-value of <0.0001.\n\n00:06:27 —\\> 00:06:34\n\nThis amounts to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone.\n\n00:06:35 —\\> 00:06:45\n\n**DR. SHAIN**: At about 30 months, 70.6% of patients had not progressed with DRd vs 55.6% of patients in the Rd group.\n\n00:06:46 —\\> 00:06:56\n\n**DR. SHAIN**: Findings from the MAIA study also demonstrated the impact of the DRd combination regimen on the overall survival in the frontline setting, which was a secondary endpoint.\n\n00:06:56 —\\> 00:07:28\n\n**DR. SHAIN**: In the follow-up analysis at approximately 5 years, MAIA demonstrated an improvement in the overall survival in the DRd arm as compared to the Rd arm. The hazard ratio was 0.68, with a 95% confidence interval of 0.53 to 0.86, and a P-value of 0.0013, representing a 32% reduction in the risk of death in patients treated in the DRd arm. Additionally, median overall survival was not reached for either arm.\n\n00:07:29 —\\> 00:07:38\n\nThus, the evidence presented so far supports choosing frontline DRd to give patients like Janice the opportunity to live longer than with Rd alone.\n\n00:07:39 —\\> 00:07:45\n\n**DR. SHAIN**: Now let’s look at the progression-free survival results for the follow-up analysis at approximately 5 years in the MAIA study.\n\n00:07:45 —\\> 00:07:52\n\nIt’s important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA.\n\n00:07:53 —\\> 00:07:58\n\nAdditionally, this analysis was not adjusted for multiplicity and conclusions should not be drawn.\n\n00:07:59 —\\> 00:08:47\n\n**DR. SHAIN**: So how does progression-free survival for DRd fare vs Rd alone after about 5 years of follow-up? Median progression-free survival was not reached in the DARZALEX® plus Rd versus 34.4 months with the Rd alone. As you can see, more patients continued living without progression in frontline DRd, with the data showing 53% of patients were progression-free vs 29% for patients on the Rd alone. The hazard ratio was 0.53, with a 95% confidence interval of 0.43 to 0.66, representing a 47% reduction in the risk of disease progression or death with DRd vs Rd alone.\n\n00:08:48 —\\> 00:08:58\n\n**DR. SHAIN**: Now let’s take a moment to review the safety profile of DRd reported in the primary analysis as I know it is a key factor when selecting frontline treatment.\n\n00:08:59 —\\> 00:09:05\n\nIn the primary analysis, safety and tolerability were evaluated at a median follow-up of about 30 months.\n\n00:09:06 —\\> 00:09:32\n\nThe most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.\n\n00:09:33 —\\> 00:09:43\n\nSerious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.\n\n00:09:44 —\\> 00:09:52\n\n**DR. SHAIN**: The most frequent hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.\n\n00:09:52 —\\> 00:10:03\n\nHematologic abnormalities were more prevalent in the DARZALEX® plus Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® plus Rd arm.\n\n00:10:04 —\\> 00:10:27\n\n**DR. SHAIN**: It’s also important to know that in the MAIA trial, infusion-related reactions of any grade with DARZALEX® plus Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification and/or discontinuation of the infusion.\n\n00:10:27 —\\> 00:10:40\n\n**DR. SHAIN**: Furthermore, in more than 2000 patients assessed through clinical trials of DARZALEX® as monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions was 37%....\n\n00:10:41 —\\> 00:10:43\n\n**DR. SHAIN**:...2% during Week 2 infusions...\n\n00:10:45 —\\> 00:10:47\n\n**DR. SHAIN**:...and 6% with subsequent infusions.\n\n00:10:48 —\\> 00:10:54\n\n**DR. SHAIN**: Like efficacy, the safety profile of DRd has been continuously evaluated in long-term follow-up analyses.\n\n00:10:55 —\\> 00:11:09\n\nIt’s important to note that treatment-emergent adverse events are reported as observed. Additionally, these analyses are not included in the Prescribing Information and have not been adjusted for multiple comparisons. Therefore, no conclusions should be drawn.\n\n00:11:10 —\\> 00:11:27\n\n**DR. SHAIN**: The results show that the safety profile remained similar for DRd in patients over about 5 years of treatment, despite a median treatment duration that was more than twice as long in the DRd group than in the Rd group (47.5 months vs 22.6 months).\n\n00:11:27 —\\> 00:11:49\n\nThe most common grade 3 or 4 treatment-emergent adverse events in more than 15% of patients in either group were neutropenia (54% in the daratumumab group vs 37% of patients in the control group), pneumonia (18% vs 9%), anemia (17% vs 22%), and lymphopenia (16% vs 11%), respectively.\n\n00:11:50 —\\> 00:12:08\n\n**DR. SHAIN**: Now, let’s look at the treatment guidelines. According to the NCCN Guidelines, daratumumab in combination with lenalidomide and dexamethasone, is a recommended Category 1 preferred therapeutic option for patients with newly diagnosed, transplant-ineligible multiple myeloma.\n\nVideo Player is loading.\n\nPlay Video\n\nPlay\n\nMute\n\nCurrent Time 0:00\n\n/\n\nDuration 28:07\n\nLoaded: 0.58%\n\n00:00\n\nStream Type LIVE\n\nSeek to live, currently behind liveLIVE\n\nRemaining Time \\-28:07\n\nShare\n\n1x\n\nPlayback Rate\n\nChapters\n\n* Chapters\n\nDescriptions\n\n* descriptions off, selected\n\nCaptions\n\n* captions settings, opens captions settings dialog\n* captions off, selected\n\nAudio Track\n\n* en (Main), selected\n\nPicture-in-Picture\n\nQuality Levels\n\n* 1080p1080pHD\n* 900p900pHD\n* 576p576p\n* 360p360p\n* 216p216p\n* AutoA, selected\n\nFullscreen\n\nThis is a modal window.\n\nBeginning of dialog window. 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This modal can be closed by pressing the Escape key or activating the close button.\n\nMAIA study on frontline treatment with DARZALEX® + Rd vs Rd alone, including primary results, and post hoc analysis in frail patients\n\nDr. Ruemu Birhiray, the founder of Indy Hematology Review, explores safety and efficacy data of the MAIA trial, including a post hoc analysis in frail patients.\n\nView video transcript\n---------------------\n\n00:00:14 —\\> 00:00:21\n\nThis is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.\n\n00:00:21 —\\> 00:00:30\n\nFaculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.\n\n00:00:31 —\\> 00:00:38\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:00:38 —\\> 00:00:53\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.\n\n00:00:53 —\\> 00:00:55\n\n**Select Important Safety Information.**\n\n00:00:55 —\\> 00:01:09\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.\n\n00:01:10 —\\> 00:01:25\n\n**Warnings and Precautions: Infusion-Related Reactions**\n\nDARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.\n\n00:01:26 —\\> 00:01:57\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:01:58 —\\> 00:02:01\n\nAdditional Important Safety Information will be reviewed later in this video.\n\n00:02:02 —\\> 00:02:22\n\n**DR BIRHIRAY:**\n\nIn the treatment of newly diagnosed, transplant-ineligible multiple myeloma, the benefits of frontline triplet DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, vs doublet Rd therapy were proven in the MAIA study.\n\n00:02:23 —\\> 00:02:25\n\n**DR BIRHIRAY:**\n\nHello, I am Dr. Birhiray.\n\n00:02:26 —\\> 00:02:38\n\n**DR BIRHIRAY:**\n\nIn this video, I will present primary data from the MAIA study first and then we will look at the post hoc subgroup analysis of the MAIA study in frail patients.\n\n00:02:40 —\\> 00:02:46\n\n**DR BIRHIRAY:**\n\nBefore I delve into the results let's spend a moment on the study design of the MAIA study.\n\n00:02:48 —\\> 00:03:07\n\nThe MAIA study is a large, randomized, open-label, multicenter, active-controlled phase 3 study comparing DRd to Rd alone in a wide range of adult patients with newly diagnosed transplant-ineligible multiple myeloma.\n\n00:03:07 —\\> 00:03:23\n\n**DR BIRHIRAY:**\n\nThe study included 737 adult patients with newly diagnosed transplant-ineligible multiple myeloma. Patients were randomized to receive either DRd or Rd alone in 28-day cycles.\n\n00:03:24 —\\> 00:03:28\n\nThe primary endpoint of the study was progression-free survival.\n\n00:03:30 —\\> 00:03:37\n\nIt's important to point out that treatment was continued until disease progression or unacceptable toxicity.\n\n00:03:38 —\\> 00:04:05\n\n**DR BIRHIRAY:**\n\nLet's take a moment to look at the baseline demographic and disease characteristics included in the study. As you can see, the baseline demographic and disease characteristics were similar between treatment groups. Patients had ECOG performance status scores ranging from 0 to 2. The study also included patients with various ISS disease stage and cytogenetic risk profiles.\n\n00:04:06 —\\> 00:04:15\n\n**DR BIRHIRAY:**\n\nIt's important to point out that the median age was 73 years, and it’s worth noting that about 50% were 75 or older.\n\n00:04:16 —\\> 00:04:21\n\n**DR BIRHIRAY:**\n\nSo, what were the efficacy and safety results in this broad patient population?\n\n00:04:22 —\\> 00:04:41\n\n**DR BIRHIRAY:**\n\nLet's examine these key findings over here. You can see from the primary results of the MAIA study that the median progression-free survival for DRd was not reached, while the median progression-free survival for Rd was 31.9 months.\n\n00:04:43 —\\> 00:05:14\n\n**DR BIRHIRAY:**\n\nThe hazard ratio was 0.56, with a 95% confidence interval that ranged from 0.43 to 0.73. This translates to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone. These results were significant with a P-value of less than 0.0001.\n\n00:05:15 —\\> 00:05:36\n\n**DR BIRHIRAY:**\n\nIn addition to efficacy, the safety of adding DARZALEX® to lenalidomide and dexamethasone was also evaluated. Adverse reactions you are seeing reflect exposure to DARZALEX® + Rd for a median treatment duration of 25.3 months as reported in the primary analysis.\n\n00:05:37 —\\> 00:06:11\n\nThe most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.\n\n00:06:12 —\\> 00:06:24\n\n**DR BIRHIRAY:**\n\nSerious adverse reactions with at least a 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.\n\n00:06:24 —\\> 00:06:39\n\n**DR BIRHIRAY:**\n\nThe most frequently reported hematologic laboratory abnormalities for a median treatment duration of 25.3 months were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.\n\n00:06:40 —\\> 00:06:53\n\nHematologic abnormalities were more prevalent in the DARZALEX® + Rd arm compared to the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® + Rd arm.\n\n00:06:54 —\\> 00:07:27\n\n**DR BIRHIRAY:**\n\nIt's also important to know that in the MAIA trial, infusion-related reactions with DARZALEX® plus Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. Infusion-related reactions of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion.\n\n00:07:29 —\\> 00:07:49\n\n**DR BIRHIRAY:**\n\nFurthermore, in over 2000 patients assessed through clinical trials of DARZALEX® as a monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions were 37%...\n\n00:07:51 —\\> 00:07:53\n\n**DR BIRHIRAY:**\n\n...2% during Week 2 infusions...\n\n00:07:55 —\\> 00:07:58\n\n**DR BIRHIRAY:**\n\n...and 6% with subsequent infusions.\n\n00:07:59 —\\> 00:08:06\n\n**DR BIRHIRAY:**\n\nLet's turn to the post hoc subgroup analysis of the frailty data that I mentioned earlier.\n\n00:08:06 —\\> 00:08:29\n\n**DR BIRHIRAY:**\n\nIt's important to consider these analyses are not included in the Prescribing Information for DARZALEX®. These analyses were conducted post hoc and were not adjusted for multiple comparisons. There are insufficient numbers of patients per subgroup to make definitive conclusions of efficacy among the subgroups.\n\n00:08:30 —\\> 00:08:39\n\n**DR BIRHIRAY:**\n\nThe frailty score was calculated retrospectively using age, Charlson Comorbidity Index, and baseline ECOG performance status score.\n\n00:08:41 —\\> 00:08:55\n\nThe frailty scores were then used to classify patients into subgroups of fit with a score of 0, intermediate with a score of 1, or frail with a score of 2 or greater.\n\n00:08:56 —\\> 00:09:24\n\nFrailty status was further simplified into 2 categories: nonfrail patients with a score of 0 or 1, which was a combination of the fit and intermediate subgroups, and frail patients with a score of greater than or equal to 2. Patients within the nonfrail and frail subgroups were further divided by ISS stage I and II versus III.\n\n00:09:25 —\\> 00:09:37\n\nIn all, for the DRd arm, there were 196 patients in the nonfrail group and 172 patients in the frail group.\n\n00:09:38 —\\> 00:09:45\n\nFor the Rd arm alone, there were 200 patients in the nonfrail group and 169 in the frail group.\n\n00:09:46 —\\> 00:09:55\n\n**DR BIRHIRAY:**\n\nBefore we go into what a frail patient looks like and the results of this post hoc analysis, let's review some of the limitations of the analysis.\n\n00:09:57 —\\> 00:10:19\n\nThe retrospective assessment of frailty score was a limitation of this study. Retrospective Charlson Comorbidity Index calculations were based on reported medical history, which may contain missing data and result in underestimating or overestimating the number of patients in each frailty subgroup.\n\n00:10:20 —\\> 00:10:43\n\nAlso, the ECOG performance status score parameter used for frailty score calculations in the study is more subjective, with susceptibility to intra- and inter-observer bias, compared with the activities of daily living and instrumental activities of daily living scales used in the International Myeloma Working Group scoring system.\n\n00:10:45 —\\> 00:11:08\n\n**DR BIRHIRAY:**\n\nAdditionally, while the frailty scale used in the study is based on parameters that are routinely assessed in clinical practice for clinical use, the use of comprehensive frailty assessment that more accurately reflect biological or functional frailty will remain important for further optimization of treatment strategies for frail patients.\n\n00:11:09 —\\> 00:11:33\n\nFinally, patients with an ECOG performance score of 3 or higher and patients with comorbidities that may interfere with the study procedures were excluded from the MAIA study; the inclusion and exclusion criteria for the study limit the generalizability of these results to more frail patients seen in clinical practice.\n\n00:11:34 —\\> 00:11:47\n\n**DR BIRHIRAY:**\n\nNow that we've established some key considerations regarding the study design, let's discuss what a frail patient may look like in your practice. In my practice, it would be someone like Samuel.\n\n00:11:50 —\\> 00:12:08\n\n**DR BIRHIRAY:**\n\nSamuel is a 78-year-old newly diagnosed, transplant-ineligible multiple myeloma patient. He has an International Staging System, or ISS, disease stage II. His Eastern Cooperative Oncology Group, or ECOG, performance status score is 2.\n\n00:12:09 —\\> 00:12:13\n\n**DR BIRHIRAY:**\n\nAdditionally, he presented with diabetes and requires assistance to get around.\n\n00:12:14 —\\> 00:12:20\n\n**DR BIRHIRAY:**\n\nLet's see how someone like Samuel aligns with patients on DRd in the post hoc analysis.\n\n00:12:22 —\\> 00:12:40\n\nIn the DRd frail group, the median age was 77 years, with 51.7% of patients having an ECOG performance score of 1 and 36.6% with an ECOG performance score of 2 or higher.\n\n00:12:41 —\\> 00:13:12\n\n**DR BIRHIRAY:**\n\nIt will be of interest to you to know that in a post hoc analysis of the MAIA study, 46.3% of the randomized patients were classified as frail, and 53.7% of patients were classified as nonfrail. Based on these data and frailty assessment criteria discussed earlier, we can agree that Samuel is truly representative of a frail patient seen in the MAIA study.\n\n00:13:13 —\\> 00:13:19\n\n**DR BIRHIRAY:**\n\nI believe you will find these following data interesting when treating patients like Samuel.\n\n00:13:20 —\\> 00:13:31\n\nThe post hoc subgroup analysis of the MAIA study found that more frail patients had not progressed when adding DARZALEX® to Rd vs Rd alone.\n\n00:13:32 —\\> 00:13:44\n\n61.5% of frail patients had not progressed with this frontline triplet regimen versus 39.5% of patients with the doublet regimen.\n\n00:13:45 —\\> 00:14:05\n\n**DR BIRHIRAY:**\n\nThe data also showed that in frail patients, there was a 38% reduction in the risk of disease progression or death with DRd vs Rd alone. The hazard ratio was 0.62 and the 95% confidence interval ranged from 0.45 to 0.85.\n\n00:14:07 —\\> 00:14:23\n\n**DR BIRHIRAY:**\n\nNow that we have seen the data of frontline DRd vs Rd alone in frail patients, you are probably asking yourself, what about the safety profile of the frontline triplet therapy in frail patients like Samuel?\n\n00:14:24 —\\> 00:14:36\n\nPlease note, all treatment-emergent adverse events are reported as observed. These analyses were conducted post-hoc and no conclusions should be drawn.\n\n00:14:36 —\\> 00:15:01\n\nThe most common Grade 3 and 4 treatment-emergent adverse events in 10% or greater of frail patients included neutropenia, lymphopenia, leukopenia, anemia, thrombocytopenia, infections including pneumonia, cataract, pulmonary embolism, hypokalemia, and hyperglycemia.\n\n00:15:01 —\\> 00:15:07\n\nFrail patients in the MAIA study had safety results similar to what was seen in the primary analysis of MAIA.\n\n00:15:09 —\\> 00:15:20\n\n**DR BIRHIRAY:**\n\nIn addition to the safety data presented in the study, here is some other safety information to consider in older patients across the DARZALEX® clinical trials.\n\n00:15:21 —\\> 00:15:51\n\nOf the 2459 patients who received DARZALEX® at the recommended dose, 38% were 65 to 74 years of age, and 15% were 75 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. The incidence of serious adverse reactions was higher in older patients than in younger patients.\n\n00:15:52 —\\> 00:16:25\n\n**DR BIRHIRAY:**\n\nAmong 1213 patients with relapsed and refractory multiple myeloma, the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Among 710 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant, the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.\n\n00:16:26 —\\> 00:16:33\n\n**DR BIRHIRAY:**\n\nBefore I present the conclusion, I would like to share the Important Safety Information about DARZALEX®.\n\n00:16:34 —\\> 00:16:36\n\n**VOICEOVER:**\n\n**IMPORTANT SAFETY INFORMATION**\n\n00:16:37 —\\> 00:16:49\n\n**CONTRAINDICATIONS** DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.\n\n00:16:50 —\\> 00:18:26\n\n**WARNINGS AND PRECAUTIONS**\n\n**Infusion-Related Reactions**\n\nDARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.\n\n00:18:27 —\\> 00:19:37\n\nWhen DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, for example 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.\n\n00:19:38 —\\> 00:20:09\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:20:10 —\\> 00:20:37\n\nTo reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.\n\n00:20:38 —\\> 00:21:01\n\nOcular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.\n\n00:21:02 —\\> 00:21:48\n\n**Interference With Serological Testing**\n\nDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.\n\n00:21:49 —\\> 00:22:15\n\n**Neutropenia and Thrombocytopenia**\n\nDARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.\n\n00:22:17 —\\> 00:22:46\n\n**Interference With Determination of Complete Response**\n\nDaratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.\n\n00:22:50 —\\> 00:23:15\n\n**Embryo-Fetal Toxicity**\n\nBased on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.\n\n00:23:18 —\\> 00:23:39\n\nThe combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.\n\n00:23:40 —\\> 00:24:16\n\n**ADVERSE REACTIONS**\n\nThe most frequently reported adverse reactions (incidence 20% or more) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (40% or more) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.\n\n00:24:18 —\\> 00:24:24\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:24:25 —\\> 00:24:39\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.\n\n00:24:41 —\\> 00:24:49\n\nIn combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant.\n\n00:24:51 —\\> 00:25:00\n\nIn combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant.\n\n00:25:01 —\\> 00:25:06\n\nIn combination with bortezomib and dexamethasone in patients who have received at least one prior therapy.\n\n00:25:07 —\\> 00:25:17\n\nIn combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.\n\n00:25:19 —\\> 00:25:29\n\nIn combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.\n\n00:25:30 —\\> 00:25:43\n\nAs monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.\n\n00:25:44 —\\> 00:25:48\n\nPlease see full Prescribing Information available on this website.\n\n00:25:49 —\\> 00:26:04\n\n**DR BIRHIRAY:**\n\nTo summarize, the primary results of the MAIA study showed that the median progression-free survival for DRd was not reached, while the median progression-free survival for Rd was 31.9 months.\n\n00:26:06 —\\> 00:26:38\n\nThe most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.\n\n00:26:39 —\\> 00:26:51\n\n**DR BIRHIRAY:**\n\nIn the post hoc sub-analysis of the MAIA study, frail patients experienced extended progression-free survival with DRd versus Rd alone.\n\n00:26:52 —\\> 00:26:59\n\nIt's important to emphasize that frailty is one consideration when choosing a frontline treatment.\n\n00:27:00 —\\> 00:27:16\n\n**DR BIRHIRAY:**\n\nTo further this point, the NCCN Guidelines recommend that frailty assessment should be considered for older patients. Given the data I've discussed in this video, I'll leave you with one final thought.\n\n00:27:17 —\\> 00:27:23\n\n**DR BIRHIRAY:**\n\nAre you ready to advance the frontline approach with DARZALEX® + Rd?\n\nVideo Player is loading.\n\nPlay Video\n\nPlay\n\nMute\n\nCurrent Time 0:00\n\n/\n\nDuration 24:24\n\nLoaded: 0.67%\n\n00:00\n\nStream Type LIVE\n\nSeek to live, currently behind liveLIVE\n\nRemaining Time \\-24:24\n\nShare\n\n1x\n\nPlayback Rate\n\nChapters\n\n* Chapters\n\nDescriptions\n\n* descriptions off, selected\n\nCaptions\n\n* captions settings, opens captions settings dialog\n* captions off, selected\n\nAudio Track\n\n* en (Main), selected\n\nPicture-in-Picture\n\nQuality Levels\n\n* 1080p1080pHD\n* 900p900pHD\n* 576p576p\n* 360p360p\n* 216p216p\n* AutoA, selected\n\nFullscreen\n\nThis is a modal window.\n\nBeginning of dialog window. Escape will cancel and close the window.\n\nTextColorWhiteBlackRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-Transparent\n\nBackgroundColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyOpaqueSemi-TransparentTransparent\n\nWindowColorBlackWhiteRedGreenBlueYellowMagentaCyanTransparencyTransparentSemi-TransparentOpaque\n\nFont Size50%75%100%125%150%175%200%300%400%\n\nText Edge StyleNoneRaisedDepressedUniformDropshadow\n\nFont FamilyProportional Sans-SerifMonospace Sans-SerifProportional SerifMonospace SerifCasualScriptSmall Caps\n\nReset restore all settings to the default valuesDone\n\nClose Modal Dialog\n\nEnd of dialog window.\n\nClose Modal Dialog\n\nThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.\n\nClose Modal Dialog\n\nThis is a modal window. This modal can be closed by pressing the Escape key or activating the close button.\n\nMAIA study of patients on frontline triplet DARZALEX® + Rd vs Rd alone, along with high-risk subgroup analysis\n\nDr. Kenneth Shain reviews the efficacy and safety of DRd vs Rd from the MAIA trial, including a subgroup analysis in patients with a high-risk cytogenetic profile.\n\nView video transcript\n---------------------\n\n00:00:14 —\\> 00:00:21\n\nThis is a nonaccredited promotional activity. This program was developed and approved by Janssen Biotech Incorporated.\n\n00:00:21 —\\> 00:00:30\n\nFaculty are compensated to present this information on behalf of the company and must do so in compliance with the US Food and Drug Administration regulations.\n\n00:00:31 —\\> 00:00:38\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:00:38 —\\> 00:00:53\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.\n\n00:00:53 —\\> 00:00:55\n\n**Select Important Safety Information**\n\n00:00:56 —\\> 00:01:09\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, to daratumumab or any of the components of the formulation.\n\n00:01:10 —\\> 00:01:25\n\n**Warnings and Precautions: Infusion-Related Reactions**\n\nDARZALEX® can cause severe and or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported.\n\n00:01:26 —\\> 00:01:57\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening Grade 4 reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:01:57 —\\> 00:02:01\n\nAdditional Important Safety Information will be reviewed later in this video.\n\n00:02:03 —\\> 00:02:14\n\nWhen considering frontline treatment options for newly diagnosed, transplant-ineligible multiple myeloma, evidence from clinical studies that evaluated a range of patient types can be an important factor.\n\n00:02:14 —\\> 00:02:16\n\n**DR. SHAIN:** Hello, I am Dr. Kenneth Shain.\n\n00:02:17 —\\> 00:02:33\n\n**DR. SHAIN:** We will look at the overall results of the MAIA trial, which studied DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, vs lenalidomide and dexamethasone, or Rd, alone. Then, we will review data in the high-risk subgroup.\n\n00:02:34 —\\> 00:02:36\n\nLet’s start with the MAIA study design.\n\n00:02:36 —\\> 00:02:50\n\n**DR. SHAIN:** MAIA is a phase 3 global, large, randomized, open-label study comparing DRd vs Rd in a wide range of adult patients with newly diagnosed, transplant-ineligible multiple myeloma.\n\n00:02:50 —\\> 00:03:49\n\n**DR. SHAIN:** The study included 737 adult patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant. Patients were randomized, 1 to 1, to receive either DARZALEX® 16 mg/kg by intravenous infusion, weekly for Cycles 1 and 2, every 2 weeks for Cycles 3 through 6, and every 4 weeks for Cycles 7 and beyond, in combination with oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone 40 mg weekly, in the DRd arm; or oral lenalidomide 25 mg daily on Days 1 through 21 and oral dexamethasone 40 mg weekly, as the active control group: the Rd arm. Baseline demographic and disease characteristics were similar between treatment groups, and treatment was continued until disease progression or unacceptable toxicity.\n\n00:03:49 —\\> 00:03:53\n\n**DR. SHAIN:** In the MAIA study the primary endpoint was progression-free survival.\n\n00:03:53 —\\> 00:04:09\n\nThe key secondary endpoints included greater than or equal to complete response rate, very good partial response rate, minimal residual disease negativity rate, overall response rate, overall survival, duration of response, and safety.\n\n00:04:09 —\\> 00:04:12\n\n**DR. SHAIN:** Let’s take a moment to look at the demographics.\n\n00:04:13 —\\> 00:04:24\n\nIn the MAIA study, 17% of the patients in the DRd arm and 16% of the patients in the Rd arm had an Eastern Cooperative Oncology Group performance score of 2 or higher.\n\n00:04:24 —\\> 00:04:33\n\n29% of the patients in the DRd arm and 30% of the patients in the Rd arm had an International Staging System stage III disease.\n\n00:04:34 —\\> 00:04:43\n\nAdditionally, 15% of the patients in the DRd arm and 14% of the patients in the Rd arm had a high-risk cytogenetic profile.\n\n00:04:44 —\\> 00:04:49 Median age of patients was 73 years, with a range of 45 to 90 years.\n\n00:04:50 —\\> 00:04:55\n\n**DR. SHAIN:** So, what were the primary efficacy and safety results in this broad patient population?\n\n00:04:55 —\\> 00:05:21\n\n**DR. SHAIN:** You can see that in the MAIA study, after about 30 months of follow-up, median PFS was not reached with DRd vs 31.9 months with Rd alone. The hazard ratio was 0.56, with a 95% confidence interval that ranged from 0.43 to 0.73. These results were significant with a P value of less than 0.0001.\n\n00:05:22 —\\> 00:05:30\n\n**DR. SHAIN:** This translates to a 44% reduction in the risk of disease progression or death with DRd vs Rd alone.\n\n00:05:30 —\\> 00:05:41\n\nAt about 30 months, 70.6% of the patients had not progressed with DRd vs 55.6% of the patients in the Rd group.\n\n00:05:42 —\\> 00:06:02\n\n**DR. SHAIN:** In addition to the efficacy, the safety of adding DARZALEX® to lenalidomide and dexamethasone was also evaluated. Adverse reactions you are seeing reflect exposure to DARZALEX® + Rd vs Rd for a median treatment duration of 25.3 months as reported in the primary analysis.\n\n00:06:02 —\\> 00:06:31\n\nThe most frequent adverse reactions reported in 20% or more of patients in the DRd arm were diarrhea, constipation, nausea, vomiting, upper respiratory tract infection, bronchitis, pneumonia, infusion-related reactions, peripheral edema, fatigue, asthenia, pyrexia, back pain, muscle spasms, dyspnea, cough, peripheral sensory neuropathy, and decreased appetite.\n\n00:06:31 —\\> 00:06:41\n\nSerious adverse reactions with at least 2% greater incidence in the DRd arm compared with the Rd arm were pneumonia, bronchitis, and dehydration.\n\n00:06:42 —\\> 00:06:51\n\n**DR. SHAIN:** The most frequently reported hematologic laboratory abnormalities were neutropenia, leukopenia, lymphopenia, thrombocytopenia, and anemia.\n\n00:06:51 —\\> 00:07:03\n\nHematologic abnormalities were more prevalent in the DARZALEX® + Rd arm compared with the Rd arm, except for anemia, which showed a lower incidence in the DARZALEX® + Rd arm.\n\n00:07:03 —\\> 00:07:24\n\n**DR. SHAIN:** It’s also important to know that infusion-related reactions, or IRRs, of any grade with DARZALEX® + Rd occurred in 41% of patients. Two percent were Grade 3 and less than 1% were Grade 4. IRRs of any grade or severity may require management by interruption, modification and/or discontinuation of the infusion.\n\n00:07:25 —\\> 00:07:38\n\n**DR. SHAIN:** Furthermore, in more than 2000 patients assessed through clinical trials of DARZALEX® as a monotherapy or combination therapy, the frequency of infusion-related reactions during Week 1 infusions was 37%...\n\n00:07:39 —\\> 00:07:42\n\n**DR. SHAIN:**...2% during Week 2 infusions...\n\n00:07:42 —\\> 00:07:45\n\n**DR. SHAIN:**...and 6% with subsequent infusions.\n\n00:07:46 —\\> 00:07:49\n\n**DR. SHAIN:** Now let’s look at the 5-year follow-up analysis of the MAIA study.\n\n00:07:50 —\\> 00:08:03\n\nIt is important to note that this information is not included in the current Prescribing Information and has not been evaluated by the FDA. Additionally, this analysis was not adjusted for multiplicity and conclusions should not be drawn.\n\n00:08:04 —\\> 00:08:16\n\n**DR. SHAIN:** At a median follow-up of about 5 years, median progression-free survival was not reached with the DARZALEX® + Rd versus 34.4 months with the Rd alone.\n\n00:08:17 —\\> 00:08:34\n\nThe hazard ratio was 0.53, with a 95% confidence interval that ranged from 0.43 to 0.66. This translates to a 47% reduction in the risk of disease progression or death with DRd versus Rd alone.\n\n00:08:35 —\\> 00:08:48\n\n**DR. SHAIN:** Now, let’s look at the 5-year safety analysis. Treatment-emergent adverse events are reported as observed. These analyses have not been adjusted for multiple comparisons, and no conclusions should be drawn.\n\n00:08:49 —\\> 00:09:04\n\nHere we can see the most frequent reported treatment-emergent adverse events of any grade in 30% or more and/or Grade 3 or 4 in 10% or more of patients in the DARZALEX® + Rd arm.\n\n00:09:04 —\\> 00:09:15\n\nThe most common treatment-emergent adverse events of Grade 3 or higher in 15% or more of patients in either group were neutropenia, pneumonia, anemia, and lymphopenia.\n\n00:09:15 —\\> 00:09:21\n\nThe safety profile remained similar for DRd over approximately 5 years of treatment.\n\n00:09:22 —\\> 00:09:40\n\n**DR. SHAIN:** The results show that the safety profile remained similar for DRd in patients over about 5 years of treatment, despite a median treatment duration that was more than twice as long as the DRd group than in the Rd group (47.5 months vs 22.6 months).\n\n00:09:41 —\\> 00:10:05\n\nThe most common grade 3 or 4 treatment-emergent adverse events in more than 15% of patients in either group were neutropenia, 54% in the daratumumab group vs 37% of patients in the control group; pneumonia, 18% vs 9%; anemia, 17% vs 22%; and lymphopenia, 16% vs 11%, respectively.\n\n00:10:05 —\\> 00:10:13\n\n**DR. SHAIN:** Cumulative Grade 3/4 infection rates were 41% for DRd vs 29% for Rd alone.\n\n00:10:14 —\\> 00:10:23\n\nThe cumulative rates of discontinuation due to treatment-emergent adverse events were 13% for the DRd group and 22% for the Rd group.\n\n00:10:24 —\\> 00:10:37\n\n**DR. SHAIN:** We just reviewed the primary and follow-up efficacy and safety data. I will now present 3-year and 5-year subgroup analyses that further examine the efficacy of DRd in the various patient types I mentioned earlier.\n\n00:10:37 —\\> 00:10:56\n\nIt is important to note that these analyses are not included in the Prescribing Information for DARZALEX®. Additionally, the high-risk subgroup analyses were prespecified and not post hoc. There are insufficient numbers of patients per subgroup to make definitive conclusions of efficacy among the subgroups.\n\n00:10:57 —\\> 00:11:00\n\n**DR. SHAIN:** Now let’s turn to the subgroup analysis.\n\n00:11:01 —\\> 00:11:13\n\nFollow-up subgroup analyses of progression-free survival were conducted at around 3 years and around 5 years in various subpopulations, including patients with high-risk cytogenetic profile.\n\n00:11:13 —\\> 00:11:32\n\n**DR. SHAIN:** Cytogenetic risk was based on fluorescence in situ hybridization (FISH) or karyotypic analysis; patients who had a high-risk cytogenetic profile had at least one high-risk abnormality: 17p deletion, 14,16 translocation, or 4,14 translocations.\n\n00:11:32 —\\> 00:11:40\n\n**DR. SHAIN:** What does a high-risk patient look like? Let’s take a look at a hypothetical patient I may see in my practice. It would be someone like Luis.\n\n00:11:41 —\\> 00:11:45\n\n**DR. SHAIN:** Luis is 76 years old and reported severe lumbar pain.\n\n00:11:45 —\\> 00:11:55\n\nHe underwent a workup that established a diagnosis of high-risk multiple myeloma, of International Staging System stage III with the presence of high-risk cytogenetics.\n\n00:11:56 —\\> 00:12:01\n\nGiven his age and his comorbidities, he was determined to be transplant ineligible.\n\n00:12:02 —\\> 00:12:08\n\n**DR. SHAIN:** How often do you come across patients who are high risk? It may be more common than we think.\n\n00:12:08 —\\> 00:12:13\n\nNearly 15% of patients with newly diagnosed multiple myeloma are considered high risk.\n\n00:12:14 —\\> 00:12:26\n\n**DR. SHAIN:** Given that these patients can be difficult to treat due to the aggressive nature of their disease and the high risk of progression, considering a frontline treatment that is effective becomes a priority.\n\n00:12:27 —\\> 00:12:33\n\n**DR. SHAIN:** Let’s examine the subgroup analysis of the MAIA study in a broad range of patient types, including high-risk patients.\n\n00:12:34 —\\> 00:12:37\n\n**DR. SHAIN:** Now, let’s dive into the data a bit deeper.\n\n00:12:38 —\\> 00:12:48\n\n**DR. SHAIN:** Note, in the subgroup analysis at approximately 3 years, PFS numerically favored DARZALEX® + Rd in most subgroups vs Rd alone.\n\n00:12:48 —\\> 00:13:02\n\n**DR. SHAIN:** And when we examine the subgroup follow-up at about 5 years, progression-free survival continued to numerically favor patients on frontline DARZALEX® + Rd vs Rd alone, including high-risk patients like Luis.\n\n00:13:03 —\\> 00:13:04\n\n**DR. SHAIN:** Now, let’s look at the 5-year data.\n\n00:13:05 —\\> 00:13:25\n\n**DR. SHAIN:** In high-risk patients, at about 3 years, median progression-free survival, or median PFS, was not reached with both DRd and Rd alone, and at about 5 years, median PFS was 45.3 months with the DRd vs 29.6 months with Rd alone.\n\n00:13:26 —\\> 00:13:35\n\n**DR. SHAIN:** Before I share the Important Safety Information for DARZALEX® and conclude the video, I wanted to reiterate a few key points from the MAIA study we just discussed.\n\n00:13:35 —\\> 00:13:44\n\nFirst, the primary results demonstrate progression-free survival benefit for frontline triplet DARZALEX® plus Rd vs doublet Rd.\n\n00:13:44 —\\> 00:13:57\n\nSecond, progression-free survival continued to numerically favor DRd in our review of the follow-ups at approximately 3 years and 5 years, both of which included high-risk patients.\n\n00:13:58 —\\> 00:14:02\n\nNow let’s review the Important Safety Information and Indications for DARZALEX®.\n\n00:14:03 —\\> 00:14:17\n\n**IMPORTANT SAFETY INFORMATION**\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity; for example, anaphylactic reactions to daratumumab or any of the components of the formulation.\n\n00:14:19 —\\> 00:15:55\n\n**WARNINGS AND PRECAUTIONS**\n\n**Infusion-Related Reactions**\n\nDARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.\n\n00:15:56 —\\> 00:17:05\n\nWhen DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days; for example, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.\n\n00:17:06 —\\> 00:17:38\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\n00:17:39 —\\> 00:18:05\n\nTo reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.\n\n00:18:06 —\\> 00:18:29\n\nOcular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.\n\n00:18:31 —\\> 00:19:16\n\n**Interference With Serological Testing**\n\nDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.\n\n00:19:17 —\\> 00:19:44\n\n**Neutropenia and Thrombocytopenia**\n\nDARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.\n\n00:19:45 —\\> 00:20:15\n\n**Interference With Determination of Complete Response**\n\nDaratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.\n\n00:20:19 —\\> 00:20:45\n\n**Embryo-Fetal Toxicity**\n\nBased on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.\n\n00:20:47 —\\> 00:21:07\n\nThe combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. 00:21:09 —\\> 00:21:45\n\n**ADVERSE REACTIONS**\n\nThe most frequently reported adverse reactions (incidence ≥20%) were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.\n\n00:21:46 —\\> 00:21:53\n\n**INDICATIONS**\n\nDARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n\n00:21:54 —\\> 00:22:07\n\nIn combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy\n\n00:22:09 —\\> 00:22:18\n\nIn combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant\n\n00:22:20 —\\> 00:22:28\n\nIn combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant\n\n00:22:29 —\\> 00:22:35\n\nIn combination with bortezomib and dexamethasone in patients who have received at least one prior therapy\n\n00:22:36 —\\> 00:22:46\n\nIn combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy\n\n00:22:48 —\\> 00:22:57\n\nIn combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor\n\n00:22:58 —\\> 00:23:12\n\nAs monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent\n\n00:23:12 —\\> 00:23:16\n\nPlease see full Prescribing Information available on this website.\n\n00:23:17 —\\> 00:23:42\n\n**DR. SHAIN:** In conclusion, what we have seen from the MAIA study is that in the treatment of newly diagnosed, transplant-ineligible multiple myeloma, the progression-free survival benefits of frontline triplet DARZALEX® plus lenalidomide and dexamethasone, also known as DRd, vs doublet Rd therapy were demonstrated at approximately 3 years, with additional follow-up at about 5 years.\n\n00:23:43 —\\> 00:23:50\n\n**DR. SHAIN:** In addition to the progression-free survival benefits, we also looked at available long-term data for subgroups of patients who are at high risk.\n\n00:23:51 —\\> 00:24:03\n\n**DR. SHAIN:** Based on the data that I have presented from the MAIA trial, are you ready to advance the frontline approach with DRd in your appropriate transplant-ineligible multiple myeloma patients?\n\nCI=confidence interval; DRd=DARZALEX® (D) + lenalidomide (R) + dexamethasone (d); DVRd=DARZALEX _FASPRO_® (D) + bortezomib (V) + lenalidomide (R) + dexamethasone (d); HR=hazard ratio; IQR=interquartile range; IV=intravenous; KOL=key opinion leader; MM=multiple myeloma; mOS=median overall survival; NCCN=National Comprehensive Cancer Network; OS=overall survival; Rd=lenalidomide (R) + dexamethasone (d); sub-Q=subcutaneous; VRd=bortezomib (V) + lenalidomide (R) + dexamethasone (d).\n\n**References:**\n\n1. DARZALEX _FASPRO_® \\[[Prescribing Information](https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf)\\]. Horsham, PA: Janssen Biotech, Inc.\n2. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. _N Engl J Med_. 2024;390(4):301-313.\n3. DARZALEX® \\[[Prescribing Information](https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf)\\]. Horsham, PA: Janssen Biotech, Inc.\n4. Moreau P, Facon T, Usmani SZ, et al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): clinical assessment of key subgroups of the phase 3 MAIA study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA.\n\n[Expand +](/#)\n\n* DARZALEX _FASPRO_®\n* DARZALEX®\n\n**INDICATIONS**\n\nDARZALEX _FASPRO_® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:\n\n* In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant\n* In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant\n* In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy\n* In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant\n* In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)\n* In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy\n* In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy\n* As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent\n\nDARZALEX _FASPRO_® as monotherapy is indicated for the treatment of adult patients with high-risk smoldering multiple myeloma.\n\n**IMPORTANT SAFETY INFORMATION**\n\n**CONTRAINDICATIONS**\n\nDARZALEX _FASPRO_® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.\n\n**WARNINGS AND PRECAUTIONS**\n\n**Hypersensitivity and Other Administration Reactions**\n\nBoth systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX _FASPRO_®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX _FASPRO_®.\n\n_Systemic Reactions_\n\nIn a pooled safety population of 1446 patients with multiple myeloma (N=1235) or light chain (AL) amyloidosis (N=193) who received DARZALEX _FASPRO_® as monotherapy or as part of a combination therapy, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3%, Grade 3: 0.8%, Grade 4: 0.1%). In patients with high-risk smoldering multiple myeloma (N=193), systemic administration-related reactions occurred in 17% of patients in AQUILA (Grade 2: 7%, Grade 3: 1%).\n\nIn all patients (N=1639), systemic administration-related reactions occurred in 7% of patients with the first injection, 0.5% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 283 systemic administration-related reactions that occurred in 135 patients, 240 (85%) occurred on the day of DARZALEX _FASPRO_® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.\n\nSevere reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.\n\nPre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX _FASPRO_®. Consider administering corticosteroids and other medications after the administration of DARZALEX _FASPRO_® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.\n\nOcular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX _FASPRO_® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX _FASPRO_®.\n\n_Local Reactions_\n\nIn this pooled safety population of 1446 patients with multiple myeloma (N=1253) or light chain amyloidosis (N=193), injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 1.1%. The most frequent (>1%) injection-site reactions were injection site erythema and injection site rash. In patients with high-risk smoldering multiple myeloma (N=193), injection-site reactions occurred in 28% of patients, including Grade 2 reactions in 3%. These local reactions occurred a median of 6 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX _FASPRO_®. Monitor for local reactions and consider symptomatic management.\n\n**Infections**\n\nDARZALEX _FASPRO_® can cause serious, life-threatening, or fatal infections. In patients who received DARZALEX _FASPRO_® in a pooled safety population including patients with smoldering multiple myeloma and light chain (AL) amyloidosis (N=1639), serious infections, including opportunistic infections, occurred in 24% of patients, Grade 3 or 4 infections occurred in 22%, and fatal infections occurred in 2.5%. The most common type of serious infection reported was pneumonia (8.5%).\n\nMonitor patients for signs and symptoms of infection prior to and during treatment with DARZALEX _FASPRO_® and treat appropriately. Administer prophylactic antimicrobials according to guidelines.\n\n**Neutropenia**\n\nDaratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX _FASPRO_® until recovery of neutrophils. In lower body weight patients receiving DARZALEX _FASPRO_®, higher rates of Grade 3-4 neutropenia were observed.\n\n**Thrombocytopenia**\n\nDaratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX _FASPRO_® until recovery of platelets.\n\n**Embryo-Fetal Toxicity**\n\nBased on the mechanism of action, DARZALEX _FASPRO_® can cause fetal harm when administered to a pregnant woman. DARZALEX _FASPRO_® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX _FASPRO_® and for 3 months after the last dose.\n\nThe combination of DARZALEX _FASPRO_® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.\n\n**Interference With Serological Testing**\n\nDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.\n\nNotify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX _FASPRO_®. Type and screen patients prior to starting DARZALEX _FASPRO_®.\n\n**Interference With Determination of Complete Response**\n\nDaratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX _FASPRO_®\\-treated patients with IgG kappa myeloma protein.\n\n**ADVERSE REACTIONS**\n\nIn multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX _FASPRO_® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, rash, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, musculoskeletal pain, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, and anemia.\n\nThe most common adverse reactions (≥20%) in patients with high-risk smoldering multiple myeloma who received DARZALEX _FASPRO_® monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions.\n\nThe most common hematology laboratory abnormalities (≥40%) with DARZALEX _FASPRO_® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.\n\n**Please** [**click here**](https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf) **to read full Prescribing Information for** **DARZALEX** _**FASPRO**_**®****.**\n\n**cp-552204v2**\n\nINDICATIONS\n\n* DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:\n* In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy\n* In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant\n* In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant\n* In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy\n* In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy\n* In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor\n* As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent\n\nIMPORTANT SAFETY INFORMATION\n\n**CONTRAINDICATIONS**\n\nDARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.\n\n**WARNINGS AND PRECAUTIONS**\n\n**Infusion-Related Reactions**\n\nDARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life‑threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision.\n\nWhen DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.\n\nPre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.\n\nTo reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.\n\nOcular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX infusion. If ocular symptoms occur, interrupt DARZALEX infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX.\n\n**Interference With Serological Testing**\n\nDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®.\n\n**Neutropenia and Thrombocytopenia**\n\nDARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.\n\n**Interference With Determination of Complete Response**\n\nDaratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.\n\n**Embryo-Fetal Toxicity**\n\nBased on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose.\n\nThe combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.\n\n**ADVERSE REACTIONS**\n\nThe most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion‑related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.\n\nPlease [**click here**](http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX-pi.pdf) to see the full Prescribing Information.\n\ncp-60862v8\n\n* [Medical Information Center](https://www.jnjmedicalconnect.com/contact-us)\n* [Site Map](/sitemap/)\n\n![Johnson & Johnson Innovative Medicine](https://components.janssenos.com/common-content/prod/logo/JNJ_Logo_Stacked_White_RGB.svg)\n\nThis site is published by Janssen Biotech, Inc., which is solely responsible for its contents. This site is intended for use by healthcare professionals of the United States and Puerto Rico. Janssen Biotech, Inc., recognizes that the internet is a global communications medium; however, laws, regulatory requirements, and medical practices for pharmaceutical products vary from market to market. The Prescribing Information included here may not be appropriate for use outside the United States and Puerto Rico.\n\nThird party trademarks used herein are trademarks of their respective owners.\n\nLast updated November 2025 | cp-233680v8\n\n* [Contact Us](https://www.jnjmedicalconnect.com/contact-us)\n* [Site map](/sitemap)\n\n* * *\n\n© Johnson & Johnson and its affiliates 2025 \n\n* [Privacy policy](https://www.janssen.com/us/privacy-policy)\n* [Legal notice](https://www.janssen.com/us/legal-notice)\n* [Cookie policy](/cookie-policy)\n* [Customize cookie settings](javascript:void\$0\$)\n\n* [Do not sell or share my personal information](https://privacyportal-cdn.onetrust.com/dsarwebform/96f23ee1-34e3-41d6-8d5a-07f0d554152b/ac3f202f-da7f-436a-b609-7f2364c326b6.html?WebsiteName=www.darzalexhcp.com)\n\n \n\nNOW APPROVED\n\n![AQUILA NOW APPROVED logo](/_next/static/media/Aquila-lock-up_DESKTOP.056e72f7.png)![AQUILA NOW APPROVED logo](/_next/static/media/Aquila-lock-up_MOBILE.eb9deff7.png)\n\nDARZALEX _FASPRO_® (daratumumab and hyaluronidase-fihj) monotherapy is the first and only FDA-approved treatment in high-risk smoldering multiple myeloma1\n\n[See the results from AQUILA](/pdfs/aquila.pdf)\n\nFDA=U.S. Food and Drug Administration.\n\n \n\n![](https://www.facebook.com/tr?id=733490791289999&ev=PageView&noscript=1)\n\n \n\nWe value your privacy\n---------------------\n\nThis website uses cookies to enhance user experience and to analyze performance and traffic on our website. 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