IMPACT OF AGE ON EFFICACY AND SAFETY OF DARATUMUMAB IN COMBINATION WITH LENALIDOMIDE AND DEXAMETHASONE (D-RD) IN PATIENTS WITH TRANSPLANT-INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): MAIA
Author(s): ,
Cyrille Hulin
Affiliations:
Department of Hematology,Hospital Haut Leveque, University Hospital,Pessac,France
,
Thierry Facon
Affiliations:
Service des Maladies du Sang,Hôpital Claude Huriez,Lille,France
,
Shaji Kumar
Affiliations:
Department of Hematology,Mayo Clinic Rochester,Rochester, MN,United States
,
Torben Plesner
Affiliations:
Vejle Hospital and University of Southern Denmark,Vejle,Denmark
,
Robert Z. Orlowski
Affiliations:
Department of Lymphoma-Myeloma,The University of Texas MD Anderson Cancer Center,Houston, TX,United States
,
Cyrille Touzeau
Affiliations:
Centre Hospitalier Universitaire,Nantes,France
,
Nizar Bahlis
Affiliations:
University of Calgary, Arnie Charbonneau Cancer Research Institute,Calgary, AB,Canada
,
Supratik Basu
Affiliations:
Royal Wolverhampton Hospitals NHS Trust,Wolverhampton,United Kingdom
,
Hareth Nahi
Affiliations:
Karolinska Institute, Department of Medicine, Division of Hematology,Karolinska University Hospital at Huddinge,Stockholm,Sweden
,
Hang Quach
Affiliations:
St. Vincent's Hospital, University of Melbourne,Melbourne,Australia
,
Hartmut Goldschmidt
Affiliations:
University Hospital Heidelberg and National Center of Tumor Diseases (NCT),Heidelberg,Germany
,
Michael O’Dwyer
Affiliations:
Department of Medicine/Haematology,NUI,Galway,Ireland
,
Gordon Cook
Affiliations:
St James’s Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds,Leeds,United Kingdom
,
Laurent Garderet
Affiliations:
Sorbonne 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
,
Christopher P. Venner
Affiliations:
Division of Medical Oncology University of Alberta,Edmonton, AB,Canada
,
Katja Weisel
Affiliations:
Department of Oncology,Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf,Hamburg,Germany
,
Noopur Raje
Affiliations:
Department of Hematology/Oncology,Massachusetts General Hospital,Boston, MA,United States
,
Benjamin Hebraud
Affiliations:
Institut Universitaire du Cancer and University Hospital,Toulouse,France
,
Karim Belhadj-Merzoug
Affiliations:
Hematology, Hopital Henri Mondor,Creteil,France
,
Lotfi Benboubker
Affiliations:
CHU de Tours, Hôpital de Bretonneau,Tours, Cedex 9,France
,
Olivier Decaux
Affiliations:
Chu Rennes, Hôpital Sud,Rennes,France
,
Salomon Manier
Affiliations:
Department of Medical Oncology,Dana-Farber Cancer Institute,Boston, MA,United States
,
Denis Caillot
Affiliations:
CHU Dijon, Hôpital Du Bocage,Dijon,France
,
Christopher Chiu
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
Maria Krevvata
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
Jianping Wang
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Rian Van Rampelbergh
Affiliations:
Janssen Research & Development,Beerse,Belgium
,
Clarissa Uhlar
Affiliations:
Janssen Research & Development,Spring House, PA,United States
,
Rachel Kobos
Affiliations:
Janssen Research & Development,Raritan, NJ,United States
,
Ming Qi
Affiliations:
Janssen Research & Development,Spring House, PA,United States
Saad Z. Usmani
Affiliations:
Levine Cancer Institute/Atrium Health,Charlotte, NC,United States
EHA Library. Hulin C. Jun 14, 2019; 266391; PF592
Cyrille Hulin
Cyrille Hulin
Contributions
Abstract

Abstract: PF592

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
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.

Aims
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.

Methods
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.

Results
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%).

Conclusion
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.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Elderly, Minimal residual disease (MRD), Monoclonal antibody, Multiple myeloma

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