The phase 3 POLLUX and CASTOR studies demonstrated superior benefit of daratumumab plus lenalidomide/dexamethasone or bortezomib/dexamethasone in relapsed/refractory multiple myeloma. Efficacy and safety of daratumumab was analyzed according to age groups of 65 to 74 years and ≥75 years. Patients received ≥1 prior line of therapy. In POLLUX, patients received lenalidomide/dexamethasone ± daratumumab (16 mg/kg weekly, cycles 1-2; every two weeks, cycles 3-6; monthly until progression). In CASTOR, patients received eight cycles of bortezomib/dexamethasone ± daratumumab (16 mg/kg weekly, cycles 1-3; every three weeks, cycles 4-8; monthly until progression). Patients aged >75 years received dexamethasone 20 mg weekly. For patients aged ≥75 years in POLLUX (median follow-up: 25.4 months), daratumumab/lenalido-mide/dexamethasone prolonged progression-free survival versus lenalido-mide/dexamethasone (median: 28.9 versus 11.4 months; hazard ratio, 0.27; 95% confidence interval, 0.10-0.69; P=0.0042) and increased overall response rate (93.1% versus 76.5%; P=0.0740). Neutropenia was the most common grade 3/4 treatment-emergent adverse event (daratumumab: 44.8%; control: 31.4%). Infusion-related reactions occurred in 12 (41.4%) patients. For patients aged ≥75 years in CASTOR (median follow-up: 19.4 months), daratumumab/bortezomib/dexamethasone prolonged progression-free survival versus bortezomib/dexamethasone (median: 17.9 versus 8.1 months; hazard ratio, 0.26; 95% confidence interval, 0.10-0.65; P=0.0022) and increased overall response rate (95.0% versus 78.8%; P=0.1134). Thrombocytopenia was the most common grade 3/4 treatment-emergent adverse event (daratumumab: 45.0%; control: 37.1%). Infusion-related reactions occurred in 13 (65.0%) patients. Similar findings were reported for patients aged 65 to 74 years in both studies. Taken together, this subgroup analysis of efficacy and safety of daratumumab was largely consistent with the overall populations.

Dana Farber Cancer Institute Harvard Medical School Boston MA USA

Department of Internal Medicine Seoul National University College of Medicine Seoul South Korea

Institute of Hematology Department of Experimental Diagnostic and Specialty Medicine University of Bologna Bologna Italy

Janssen Global Medical Affairs Horsham PA USA

Janssen Research and Development LLC Raritan NJ USA

Janssen Research and Development LLC Spring House PA USA

Levine Cancer Institute Atrium Health Charlotte NC USA

Malignant Haematology and Stem Cell Transplantation Service Alfred Health Monash University Melbourne Australia

Nagoya City University Graduate School of Medical Sciences Nagoya Japan

National and Kapodistrian University of Athens Athens Greece

Service d'Hématologie et Thérapie Cellulaire Hôpital Bretonneau Centre Hospitalier Régional Universitaire Tours France

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

Tom Baker Cancer Center University of Calgary Calgary Alberta Canada

University Hospital Brno Brno Czech Republic

University Hospital of Salamanca IBSAL Salamanca Spain

University Medical Center of Hamburg Eppendorf Hamburg Germany

Winship Cancer Institute Emory University Atlanta GA USA

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Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis

Carfilzomib, Pomalidomide, and Dexamethasone As Second-line Therapy for Lenalidomide-refractory Multiple Myeloma

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma

Intercellular Mitochondrial Transfer in the Tumor Microenvironment

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ClinicalTrials.gov
NCT02076009, NCT02136134