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Nahi, Hareth

https://orcid.org/0000-0003-4711-5094

Mayo Clinic

Karolinska University Hospital

Citations 22

Sustained Improvement in Health‐Related Quality of Life in Transplant‐Ineligible Newly Diagnosed Multiple Myeloma Treated With Daratumumab, Lenalidomide, and Dexamethasone: MAIA Final Analysis of Patient‐Reported Outcomes
Plesner, Torben , Kumar, Shaji, Hulin, Cyrille , Orlowski, Robert Z. , Nahi, Hareth , Delforge, Michel, Karlin, Lionel, Arnulf, Bertrand , Gupta‐Werner, Niodita , Kaila, Shuchita, Pei, Huiling , Matt, Kathryn, Gries, Katharine S. , Carson, Robin, Borgsten, Fredrik, Nahi, Hareth , Roussel, Murielle , Arnulf, Bertrand , Orlowski, Robert Z. , Perrot, Aurore , Facon, Thierry T.F. , Usmani, Saad Z. , Kumar, Shaji , Bahlis, Nizar Jacques , Mollee, Peter , Ramasamy, Karthik , Roussel, Murielle , Jaccard, Arnaud , Karlin, Lionel , Chari, Ajai , Wang, George C. , Weisel, Katja C

European Journal of Haematology | February 14, 2025 | Volume: 114 | Issue: 5 | Pages: 883-889

10.1111/ejh.14392 Get It

ABSTRACTObjectivesThis final post hoc analysis evaluated patient‐reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D‐Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5‐month follow‐up in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups.MethodsKey scales from the EORTC QLQ‐C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression.ResultsThe intent‐to‐treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D‐Rd‐treated patients showed improvements from baseline that were sustained over 5 years in the intent‐to‐treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D‐Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16–2.91]), physical functioning (1.93 [1.18–3.14]), pain (1.41 [0.90–2.22]), and fatigue (2.00 [1.24–3.23]). Greater proportions of patients with bone lesions improved with D‐Rd versus Rd on GHS and physical functioning.ConclusionsIn transplant‐ineligible patients with NDMM, D‐Rd improved health‐related quality of life over a 5‐year period versus Rd. Trial Registration: ClinicalTrials.gov: NCT02252172
P16 HEALTH-RELATED QUALITY OF LIFE FOR FRAIL TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH DARATUMUMAB, LENALIDOMIDE AND DEXAMETHASONE: SUBGROUP ANALYSIS OF MAIA TRIAL
Plesner, Torben , Kumar, Shaji , Hulin, Cyrille , Delforge, Michel, Karlin, Lionel, Arnulf, Bertrand , Pei, Huiling , Kaila, S., Matt, K., Gries, Katharine S. , Carson, Robin, Borgsten, F., Facon, Thierry T.F. , Usmani, Saad Z. , Bahlis, Nizar Jacques , Orlowski, Robert Z. , Nahi, Hareth , Mollee, Peter , Ramasamy, Karthik , Roussel, Murielle , Jaccard, Arnaud , Karlin, Lionel , Chari, Ajai , Gupta, Neeraj , Matt, K., Weisel, Katja C , Perrot, Aurore

HemaSphere | November 16, 2023 | Volume: 7 | Issue: S2 | Pages: 18-19

10.1097/01.hs9.0000936192.21618.f2 Get It

P09 DARATUMUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE (D-RD) VERSUS LENALIDOMIDE AND DEXAMETHASONE (RD) ALONE IN TRANSPLANT-INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): UPDATED ANALYSIS OF THE PHASE 3 MAIA STUDY
Kumar, Shaji , Facon, T., Plesner, Torben , Hulin, Cyrille , Goldschmidt, Hartmut , Venner, Christopher P. , Tiab, Mourad, Macro, Margaret , Leleu, Xavier , Pei, Huiling , Krevvata, Maria, Carson, Robin, Borgsten, F., Weisel, Katja C , Moreau, Philippe , Bahlis, Nizar Jacques , Orlowski, Robert Z. , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Perrot, Aurore , Raje, Noopur , Frenzel, Laurent , Usmani, Saad Z.

HemaSphere | November 16, 2023 | Volume: 7 | Issue: S2 | Pages: 14-15

10.1097/01.hs9.0000936164.84357.ed Get It

Plain Language Summary of the MAIA Study of Daratumumab Plus Lenalidomide and Dexamethasone for the Treatment of People with Newly Diagnosed Multiple Myeloma
Kumar, Shaji , Plesner, Torben , Orlowski, Robert Z. , Hulin, Cyrille , Goldschmidt, Hartmut , Macro, Margaret , Leleu, Xavier , Wang, Jianping , Rampelbergh, Rian Van , Uhlar, Clarissa, Vermeulen, Jessica, Duran, Joana , Borgsten, Fredrik, Usmani, Saad Z. , Orlowski, Robert Z. , Usmani, Saad , Facon, Thierry T.F. , Moreau, Philippe , Bahlis, Nizar Jacques , Basu, Supratik , Nahi, Hareth , Quach, Hang , Perrot, Aurore , Weisel, Katja C , Raje, Noopur , Frenzel, Laurent

Future Oncology | May 22, 2023 | Volume: 19 | Issue: 13 | Pages: 887-895

10.2217/fon-2023-0082 Get It

Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Transplant-Ineligible Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM): Clinical Assessment of Key Subgroups of the Phase 3 Maia Study
Usmani, Saad Z. , Plesner, Torben , Hulin, Cyrille , Goldschmidt, Hartmut , Venner, Christopher P. , Tiab, Mourad, Macro, Margaret , Leleu, Xavier , Pei, Huiling , Krevvata, Maria, Carson, Robin, Borgsten, Fredrik, Kumar, Shaji , Usmani, Saad , Moreau, Philippe , Facon, Thierry T.F. , Bahlis, Nizar Jacques , Raje, Noopur , Orlowski, Robert Z. , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Perrot, Aurore , Weisel, Katja C , Frenzel, Laurent

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 7297-7300

10.1182/blood-2022-163494 Get It

Daratumumab Plus Lenalidomide and Dexamethasone in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma: Maia Age Subgroup Analysis
Kumar, Shaji , Plesner, Torben , Hulin, Cyrille , Venner, Christopher P. , Tiab, Mourad, Macro, Margaret , Leleu, Xavier , Pei, Huiling , Carson, Robin, Borgsten, Fredrik, Goldschmidt, Hartmut , Facon, Thierry T.F. , Weisel, Katja C , Usmani, Saad Z. , Moreau, Philippe , Orlowski, Robert Z. , Bahlis, Nizar Jacques , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Perrot, Aurore , Raje, Noopur , Frenzel, Laurent

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 10133-10136

10.1182/blood-2022-163555 Get It

Health-Related Quality of Life for Frail Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Lenalidomide and Dexamethasone: Subgroup Analysis of MAIA Trial
Plesner, Torben , Usmani, Saad Z. , Kumar, Shaji , Hulin, Cyrille , Roussel, Murielle , Delforge, Michel, Karlin, Lionel , Arnulf, Bertrand , Pei, Huiling , Gupta, Niodita, Kaila, Shuchita, Matt, Kathryn, Gries, Katharine S. , Carson, Robin, Borgsten, Fredrik, Usmani, Saad , Roussel, Murielle , Perrot, Aurore , Facon, Thierry T.F. , Bahlis, Nizar Jacques , Orlowski, Robert Z. , Nahi, Hareth , Mollee, Peter , Ramasamy, Karthik , Jaccard, Arnaud , Chari, Ajai , Weisel, Katja C

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 1142-1145

10.1182/blood-2022-165524 Get It

Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma (NDMM): Updated Analysis of the Phase 3 Maia Study
Kumar, Shaji , Plesner, Torben , Hulin, Cyrille , Goldschmidt, Hartmut , Venner, Christopher P. , Tiab, Mourad, Macro, Margaret , Leleu, Xavier , Pei, Huiling , Krevvata, Maria, Carson, Robin, Borgsten, Fredrik, Moreau, Philippe , Bahlis, Nizar Jacques , Facon, Thierry T.F. , Orlowski, Robert Z. , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Perrot, Aurore , Weisel, Katja C , Raje, Noopur , Frenzel, Laurent , Usmani, Saad Z.

Blood | November 28, 2022 | Volume: 140 | Issue: Supplement 1 | Pages: 10150-10153

10.1182/blood-2022-163335 Get It

Sustained Improvement in Health-Related Quality of Life in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone: Update of the Phase 3 MAIA Tria
Kumar, Shaji , Plesner, Torben , Hulin, Cyrille , Goldschmidt, Hartmut , Venner, Chris , Mace, Joseph R., Tiab, Mourad, Macro, M. , Leleu, Xavier , Fastenau, John , Gries, Katharine S. , Ho, Kai Fai, Mistry, Pankaj , Tromp, Brenda, Delioukina, Maria , Vermeulen, Jessica, Perrot, Aurore , Facon, Thierry T.F. , Orlowski, Robert Z. , Moreau, Philippe , Bahlis, Nizar Jacques , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Weisel, Katja C , Raje, Noopur , Frenzel, Laurent , Liu, Kevin , Usmani, Saad Z.

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 1655-1655

10.1182/blood-2021-144421 Get It

Abstract Introduction: Multiple myeloma (MM) is a chronic hematologic malignancy with a high symptom burden that can have a substantial negative impact on patients' (pts) health-related quality of life (HRQoL). The introduction of novel triplet regimens for newly diagnosed MM (NDMM) has extended progression-free survival (PFS) and overall survival (OS); however, adverse events and demanding administration and monitoring schedules have a further negative effect on HRQoL, especially among pts who are transplant ineligible (TIE) due to older age and/or frailty. Optimizing initial treatment is particularly important in older pts, many of whom receive only 1 line of therapy. The phase 3 MAIA trial compared daratumumab, lenalidomide, and dexamethasone (D-Rd) vs lenalidomide and dexamethasone (Rd) in TIE pts with NDMM. At a median follow-up of 28 months, D-Rd significantly prolonged PFS and was associated with faster and sustained clinically meaningful improvements in patient-reported outcomes (PROs) vs Rd. Results of an updated analysis with longer follow-up recently confirmed a significant benefit in OS with D-Rd vs Rd as well as a continued significant PFS benefit and higher rates of complete response or better and very good partial response or better. Here we present an update of the HRQoL analysis with additional follow-up. Methods: MAIA (NCT02252172) is a randomized, open-label, active controlled, multicenter, phase 3 study of TIE pts with NDMM who were randomly assigned 1:1 to receive D-Rd or Rd until disease progression (PD) or unacceptable toxicity. PROs were recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EQ-5D-5L visual analog scale. EORTC QLQ-C30 has 30 items comprising 5 functional scales (physical, role, emotional, cognitive, and social functioning), 1 global health status (GHS) scale, 3 symptom scales (fatigue, nausea and vomiting, and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Questionnaires were completed at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, and every 6 months thereafter until PD. Analyses were conducted on all pts with a baseline and ≥1 post-baseline PRO assessment. Pts were censored at PD or discontinuation of study treatment. Thresholds for meaningful improvement and worsening were defined a priori based on published literature (≥10-point change). Treatment effect was analyzed using a mixed-effects model for repeated measurements including baseline value, visit, treatment, visit by treatment interaction, and randomization stratification factors as fixed effects and individual subject as random effect. Results: At a median follow-up of 56.2 months, discontinuation rates were lower with D-Rd than Rd (56.8% vs 80.8%). For GHS, physical functioning, fatigue, pain, and dyspnea, PROs that are particularly relevant to pts with MM, a numerically greater proportion of pts achieved a meaningful improvement with D-Rd vs Rd (Table 1). Differences were significant for physical functioning, fatigue, and dyspnea. The proportion of pts achieving a meaningful worsening on therapy was similar in both treatment groups (Table 1). The median time to improvement was numerically shorter with D-Rd vs Rd for physical functioning and pain and with Rd vs D-Rd for GHS and fatigue; differences were not significant (Table 2). The median time to worsening of fatigue was similar between groups, numerically longer for D-Rd vs Rd for GHS, and significantly longer with D-Rd than Rd for physical functioning, pain, and dyspnea (Table 2). Median time to worsening of pain with D-Rd vs Rd was 39.43 vs 17.97 months, reflective of an additional ~21 months without worsening pain among pts treated with D-Rd. Between-group differences for least squares mean change from baseline for these 5 PROs favored D-Rd vs Rd at all assessment time points except cycle 3 for physical functioning and cycle 6 for fatigue; differences were significant at ≥1 timepoint for each scale. Conclusions: These updated PRO analyses from the MAIA study demonstrate sustained and clinically meaningful improvements in HRQoL with D-Rd vs Rd with almost 5 years of follow-up. These results are consistent with the clinical benefits of superior PFS, OS, and deep responses observed with D-Rd compared with Rd and support the use of D-Rd in older pts. Figure 1 Figure 1. Disclosures Perrot: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kumar: Roche-Genentech: Consultancy, Research Funding; Novartis: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Bluebird Bio: Consultancy; Tenebio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Antengene: Consultancy, Honoraria; Oncopeptides: Consultancy; Beigene: Consultancy; BMS: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Plesner: Takeda: Research Funding; Oncopeptides: Other: Advisor, Research Funding; Genentech: Other: Advisor, Research Funding; CSL Behring: Other: Advisor; AbbVie: Other: Advisor, Research Funding; Celgene: Other: Advisor, Research Funding; Janssen: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Oncopeptides: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene BMS: Honoraria; Amgen: Honoraria; Abbvie: Honoraria. Bahlis: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Genentech: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: Takeda: Honoraria; Sanofi: Honoraria; Celgene/BMS: Honoraria; Janssen: Honoraria; abbvie: Honoraria. Quach: CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Goldschmidt: Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Incyte: Research Funding; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Johns Hopkins University: Other: Grant; Molecular Partners: Research Funding; MSD: Research Funding; Mundipharma: Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Takeda: Consultancy, Research Funding; Adaptive Biotechnology: Consultancy; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; GSK: Honoraria; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. O'Dwyer: ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Bristol Myers Squibb: Research Funding. Venner: BMS: Honoraria; Amgen: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria. Weisel: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Sanofi: Honoraria; GSK: Honoraria; Takeda: Honoraria, Other: Travel accomodation, Research Funding; Janssen: Honoraria, Other: Travel accomodation, Research Funding; Celgen/BMS: Honoraria. Leleu: Sanofi: Honoraria; Takeda: Honoraria, Other: Non-financial support; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Gilead Sciences: Honoraria; Celgene: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria. Liu: Janssen: Current Employment, Current equity holder in publicly-traded company. Fastenau: Janssen: Current Employment, Current equity holder in publicly-traded company. Gries: Janssen: Current Employment, Current holder of individual stocks in a privately-held company. Ho: DRG Abacus: Consultancy; Janssen: Consultancy; Emalex Biosciences: Consultancy. Mistry: Janssen: Current Employment, Current equity holder in publicly-traded company. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment. Vermeulen: Janssen: Current Employment, Current equity holder in publicly-traded company. Usmani: Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau.
Efficacy of Daratumumab, Lenalidomide, and Dexamethasone in Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma and Impaired Renal Function from the Phase 3 Maia Study Based on Lenalidomide Starting Dose
Kumar, Shaji , Plesner, Torben , Hulin, Cyrille , Goldschmidt, Hartmut , Venner, Chris , Mace, Joseph R., Tiab, Mourad, Macro, Margaret , Leleu, Xavier , Pei, Huiling , Rampelbergh, Rian Van , Tromp, Brenda, Delioukina, Maria , Usmani, Saad Z. , Orlowski, Robert Z. , Moreau, Philippe , Bahlis, Nizar Jacques , Basu, Supratik , Nahi, Hareth , Quach, Hang , O’Dwyer, Michael , Perrot, Aurore , Weisel, Katja C , Raje, Noopur , Frenzel, Laurent , Facon, Thierry T.F.

Blood | November 23, 2021 | Volume: 138 | Issue: Supplement 1 | Pages: 1646-1646

10.1182/blood-2021-146940 Get It

Abstract Introduction: The phase 3 MAIA study (NCT02252172) evaluated the addition of daratumumab (D) to lenalidomide and dexamethasone (Rd) in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (NDMM). At a median follow-up of 56.2 months, D-Rd prolonged progression-free survival (PFS) and overall survival (OS) versus Rd alone, despite almost half of the pts in the Rd arm who received subsequent therapy receiving a daratumumab-containing regimen as any subsequent line of therapy (Facon T, et al. Presented at: European Hematology Association 2021 Virtual Congress. Abstract LB1901). Approximately 20% to 50% of pts with MM have baseline renal impairment that can affect the choice and efficacy of therapy (Dimopoulos MA, et al. Journal of Clinical Oncology. 2016;34[13]:1544-1557). Here, we report results from MAIA for D-Rd vs Rd in pts with impaired renal function based on lenalidomide starting dose at a median follow-up of 56.2 months. Methods: Pts with NDMM ineligible for high-dose chemotherapy and autologous stem-cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to receive D-Rd or Rd. Pts in both arms received 28-day cycles of oral Rd (R: 25 mg [10 mg recommended if creatinine clearance (CrCl) was 30-50 mL/min] on Days 1-21; d: 40 mg [20 mg if aged &gt;75 years or body-mass index &lt;18.5 kg/m 2] on Days 1, 8, 15, 22). Pts in the D-Rd arm also received intravenous D (16 mg/kg once weekly for Cycles 1-2, once every 2 weeks for Cycles 3-6, and once every 4 weeks thereafter). Pts in both arms were treated until disease progression or unacceptable safety events. The primary endpoint was PFS, and a secondary endpoint was OS. Renal impairment was defined as a baseline CrCl of ≤60 mL/min. Results: 737 pts were randomized (D-Rd, n=368; Rd, n=369); 162 (44%) pts in the D-Rd arm and 142 (38%) pts in the Rd arm had renal impairment as defined. At a median follow-up of 56.2 months, in pts with renal impairment who received a lenalidomide starting dose of 25 mg (25 mg subgroup; D-Rd, n=60 [37%]; Rd, n=62 [44%]), a PFS and OS advantage was observed with D-Rd versus Rd (Table). In pts with renal impairment who received a lenalidomide starting dose of &lt;25 mg (&lt;25 mg subgroup; D-Rd, n=98 [60%]; Rd, n=75 [53%]), median PFS and OS were prolonged with D-Rd versus Rd (Table). Among pts in the 25 mg subgroup who died (D-Rd, n=12; Rd, n=29), disease progression was the primary cause of death in 6 (50%) pts in the D-Rd arm and 10 (34%) pts in the Rd arm. Among pts in the &lt;25 mg subgroup who died (D-Rd, n=44; Rd, n=37), disease progression was the primary cause of death in 16 (36%) pts in the D-Rd arm and 11 (30%) pts in the Rd arm. Conclusion: After ~5 years of follow-up, D-Rd showed a PFS improvement versus Rd in transplant-ineligible pts with NDMM and renal impairment regardless of lenalidomide starting dose. An OS advantage for D-Rd versus Rd was observed in pts with renal impairment who received a lenalidomide starting dose of 25 mg; in pts with renal impairment who received a lenalidomide starting dose of &lt;25 mg, median OS was prolonged for D-Rd versus Rd, but the OS benefit was less pronounced. Overall, among pts with renal impairment, PFS and OS benefits of D-Rd versus Rd were observed regardless of lenalidomide starting dose; however, dose recommendations per the lenalidomide prescribing information should be followed. Many transplant-ineligible pts with NDMM may not receive a second line of therapy; our results support the frontline use of D-Rd to provide prolonged disease control in transplant-ineligible pts with NDMM and renal impairment. Figure 1 Figure 1. Disclosures Usmani: Abbvie: Consultancy; Array BioPharma: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; GSK: Consultancy, Research Funding; EdoPharma: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Merck: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; SkylineDX: Consultancy, Research Funding; Takeda: Consultancy, Research Funding, Speakers Bureau; Janssen Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau. Kumar: Novartis: Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Merck: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Consultancy; Antengene: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Carsgen: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tenebio: Research Funding; Oncopeptides: Consultancy; Bluebird Bio: Consultancy; Roche-Genentech: Consultancy, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding. Plesner: CSL Behring: Other: Advisor; Genentech: Other: Advisor, Research Funding; Oncopeptides: Other: Advisor, Research Funding; Takeda: Research Funding; Celgene: Other: Advisor, Research Funding; AbbVie: Other: Advisor, Research Funding; Janssen: Other: Advisor, Research Funding; Genmab: Research Funding. Orlowski: Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, EcoR1 Capital LLC, Genzyme, GSK Biologicals, Janssen Biotech, Karyopharm Therapeutics, Inc., Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, Inc., Sanofi-Aventis, and Takeda P: Consultancy, Honoraria; CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Other: Clinical research funding; Asylia Therapeutics, Inc., BioTheryX, Inc., and Heidelberg Pharma, AG.: Other: Laboratory research funding; Asylia Therapeutics, Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Amgen, Inc., BioTheryX, Inc., Bristol-Myers Squibb, Celgene, Forma Therapeutics, Genzyme, GSK Biologicals, Janssen Biotech, Juno Therapeutics, Karyopharm Therapeutics, Inc., Kite Pharma, Neoleukin Corporation, Oncopeptides AB, Regeneron Pharmaceuticals, I: Membership on an entity's Board of Directors or advisory committees. Moreau: Abbvie: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Celgene BMS: Honoraria; Oncopeptides: Honoraria. Bahlis: Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Genentech: Consultancy; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Nahi: XNK Therapeutics AB: Consultancy. Hulin: Janssen: Honoraria; Celgene/BMS: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; abbvie: Honoraria. Quach: GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Goldschmidt: Takeda: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Novartis: Honoraria, Research Funding; Dietmar-Hopp-Foundation: Other: Grant; Mundipharma: Research Funding; MSD: Research Funding; Molecular Partners: Research Funding; Johns Hopkins University: Other: Grant; Janssen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Celgene: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; BMS: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; Chugai: Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding; GSK: Honoraria; Incyte: Research Funding; Adaptive Biotechnology: Consultancy; Amgen: Consultancy, Honoraria, Other: Grants and/or Provision of Investigational Medicinal Product, Research Funding. O'Dwyer: ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Janssen: Consultancy. Perrot: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria. Venner: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Celgene: Research Funding; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Amgen: Research Funding. Weisel: Novartis: Honoraria; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; Roche: Honoraria; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Macro: Janssen: Honoraria, Other: Travel accomodation, Research Funding; GSK: Honoraria; Sanofi: Honoraria; Celgen/BMS: Honoraria; Takeda: Honoraria, Other: Travel accomodation, Research Funding. Leleu: Bristol-Myers Squibb: Honoraria; Carsgen Therapeutics Ltd: Honoraria; Celgene: Honoraria; Gilead Sciences: Honoraria; Janssen-Cilag: Honoraria; Karyopharm Therapeutics: Honoraria; Merck: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria; Oncopeptides: Honoraria; Pierre Fabre: Honoraria; Roche: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Other: Non-financial support. Pei: Janssen: Current Employment, Current equity holder in publicly-traded company. Van Rampelbergh: Janssen: Current Employment. Tromp: Janssen: Current Employment, Current equity holder in publicly-traded company. Delioukina: Janssen: Current Employment.