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Plasma Cell DIsorders
Ferrata Storti Foundation
Haematologica 2020 Volume 105(2):468-477
Daratumumab-based regimens are highly effective and well tolerated in relapsed or refractory multiple myeloma regardless of patient age: subgroup analysis of the phase 3 CASTOR and POLLUX studies
Maria-Victoria Mateos,1 Andrew Spencer,2 Ajay K. Nooka,3 Ludek Pour,4 Katja Weisel,5 Michele Cavo,6 Jacob P. Laubach,7 Gordon Cook,8 Shinsuke Iida,9 Lotfi Benboubker,10 Saad Z. Usmani,11 Sung-Soo Yoon,12 Nizar J. Bahlis,13 Christopher Chiu,14 Jon Ukropec,15 Jordan M. Schecter,16 Xiang Qin,14 Lisa O’Rourke,14 and Meletios A. Dimopoulos17
1University Hospital of Salamanca/IBSAL, Salamanca, Spain; 2Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, Australia; 3Winship Cancer Institute, Emory University, Atlanta, GA, USA; 4University Hospital Brno, Brno, Czech Republic; 5University Medical Center of Hamburg-Eppendorf, Hamburg, Germany; 6Institute of Hematology Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 7Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 8St James’s Institute of Oncology, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom; 9Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; 10Service d’Hématologie et Thérapie Cellulaire, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours, France; 11Levine Cancer Institute/Atrium Health, Charlotte, NC, USA; 12Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; 13Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada; 14Janssen Research and Development, LLC, Spring House, PA, USA; 15Janssen Global Medical Affairs, Horsham, PA, USA; 16Janssen Research & Development, LLC, Raritan, NJ, USA and 17National and Kapodistrian University of Athens, Athens, Greece
ABSTRACT
The phase 3 POLLUX and CASTOR studies demonstrated superior benefit of daratumumab plus lenalidomide/dexamethasone or borte- zomib/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 ± daratumum- ab (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 progres- sion-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.
Correspondence:
MARIA-VICTORIA MATEOS
mvmateos@usal.es
Received: January 23, 2019. Accepted: June 20, 2019. Pre-published: June 20, 2019.
doi:10.3324/haematol.2019.217448
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