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Hulin, C.1; Facon, T.2; Kumar, S.3; Plesner, T.4; Orlowski, R. Z.5; Touzeau, C.6; Bahlis, N.7; Basu, S.8; Nahi, H.9; Quach, H.10; Goldschmidt, H.11; O'Dwyer, M.12; Cook, G.13; Garderet, L.14; Venner, C. P.15; Weisel, K.16; Raje, N.17; Hebraud, B.18; Belhadj-Merzoug, K.19; Benboubker, L.20; Decaux, O.21; Manier, S.22; Caillot, D.23; Chiu, C.24; Krevvata, M.24; Wang, J.25; Van Rampelbergh, R.26; Uhlar, C.24; Kobos, R.25; Qi, M.24; Usmani, S. Z.27

doi: 10.1097/01.HS9.0000560656.54765.eb
Poster Session I: Myeloma and other monoclonal gammopathies - Clinical

1Department of Hematology, Hospital Haut Leveque, University Hospital, Pessac

2Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France

3Department of Hematology, Mayo Clinic Rochester, Rochester, MN, United States

4Vejle Hospital and University of Southern Denmark, Vejle, Denmark

5Department of Lymphoma-Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, United States

6Centre Hospitalier Universitaire, Nantes, France

7University of Calgary, Arnie Charbonneau Cancer Research Institute, Calgary, AB, Canada

8Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, United Kingdom

9Karolinska Institute, Department of Medicine, Division of Hematology, Karolinska University Hospital at Huddinge, Stockholm, Sweden

10St. Vincent's Hospital, University of Melbourne, Melbourne, Australia

11University Hospital Heidelberg and National Center of Tumor Diseases (NCT), Heidelberg, Germany

12Department of Medicine/Haematology, NUI, Galway, Ireland

13St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom

14Sorbonne Université, INSERM, UMR_S 938, Centre de Recherche Saint-Antoine, Team Proliferation and Differentiation of Stem Cells, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Département d'Hématologie et de Thérapie Cellulaire, Paris, France

15Division of Medical Oncology University of Alberta, Edmonton, AB, Canada

16Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

17Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, United States

18Institut Universitaire du Cancer and University Hospital, Toulouse

19Hematology, Hopital Henri Mondor, Creteil

20CHU de Tours, Hôpital de Bretonneau, Tours, Cedex 9

21Chu Rennes, Hôpital Sud, Rennes, France

22Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, United States

23CHU Dijon, Hôpital Du Bocage, Dijon, France

24Janssen Research & Development, Spring House, PA

25Janssen Research & Development, Raritan, NJ, United States

26Janssen Research & Development, Beerse, Belgium

27Levine Cancer Institute/Atrium Health, Charlotte, NC, United States

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Elderly patients with MM often have low performance status, reduced organ function, and increased comorbidities, all of which affect their ability to tolerate MM treatment and may result in lower efficacy. In the recently reported phase 3 MAIA study, D-Rd significantly reduced the risk of progression or death by 44% vs lenalidomide and dexamethasone (Rd) alone in transplant-ineligible NDMM patients, and demonstrated tolerability consistent with previously reported studies of daratumumab and Rd alone.

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To examine the impact of age on efficacy and safety of D-Rd vs Rd in this population, a subgroup analysis was conducted in patients <75 and ≥75 years of age.

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Transplant-ineligible NDMM patients were randomized 1:1 to Rd with or without daratumumab; stratification was based on age (<75 vs ≥75 y), ISS (I, II, III), and region (North America vs Other). Patients received 28-day cycles of either lenalidomide 25 or 10 mg (based on renal function) PO QD on Days 1-21 and either dexamethasone 40 or 20 mg (based on age or BMI) PO/IV weekly until progression. In the D-Rd arm, patients received daratumumab 16 mg/kg IV QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter until progression. PFS was the primary endpoint.

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Among 737 randomized patients (D-Rd, n = 368; Rd, n = 369), 321 (44%) were ≥75 y of age. A higher proportion of patients in the D-Rd arm received a lower starting dose of lenalidomide (10 mg) compared with the Rd arm (30.8% vs 22.7%), and a lower relative median dose intensity for lenalidomide (<75 y: 79% vs 93%; ≥75 y: 66% vs 89%). After median follow-up of 28 mo, significant PFS benefit of D-Rd vs Rd was maintained in both <75 and ≥75 y subgroups (<75: median not reached [NR] vs 33.7 mo; HR 0.50; 95% CI 0.35-0.71; ≥75 y: median NR vs 31.9 mo; HR 0.63; 95% CI 0.44-0.92; Figure). Overall response rate (<75: 95% vs 82%; ≥75 y: 90% vs 81%), rate of complete response or better (<75: 52% vs 25%; ≥75 y: 41% vs 25%), rate of very good partial response or better (<75: 81% vs 53%; ≥75 y: 77% vs 53%), and minimal residual disease-negative rate (10-5 threshold; <75: 28% vs 7%; ≥75 y: 19% vs 8%) remained higher with D-Rd vs Rd in both age subgroups. Most common (≥10%; D-Rd/Rd) grade 3/4 TEAEs in <75 y patients were neutropenia (43%/31%), pneumonia (13%/6%), lymphopenia (12%/10%), leukopenia (10%/4%), and anemia (9%/18%). Most common (≥10%; D-Rd/Rd) grade 3/4 TEAEs in ≥75 y patients were neutropenia (60%/41%), lymphopenia (19%/12%), anemia (16%/22%), pneumonia (15%/10%), leukopenia (12%/6%), and thrombocytopenia (8%/11%). Fewer patients receiving D-Rd vs Rd discontinued treatment due to TEAEs (<75 y: 5% vs 12%; ≥75 y: 10% vs 21%); discontinuation rates due to infections for D-Rd vs Rd were low in both age groups (<75 y: 1% vs 1%; ≥75 y: 0% vs 2%). A higher proportion of ≥75 y patients discontinued lenalidomide due to TEAEs compared with <75 y patients (≥75 y: 29% vs 22%; <75 y: 15% vs 13%).



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D-Rd patients received less lenalidomide compared with the Rd group regardless of age. Efficacy of D-Rd in <75 and ≥75 y patients was consistent with the ITT population, and D-Rd demonstrated a manageable safety profile regardless of age. Together with the phase 3 ALCYONE study, these studies confirm the clinical benefit of daratumumab plus standard-of-care in transplant-ineligible NDMM patients ≥75 y of age.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.