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

• Type of Material: Article
• Authors: Maria-Victoria Mateos, Hospital Clínico Universitario de Salamanca; Andrew Spencer, Monash University; Ajay Nooka, Emory University; Ludek Pour, University Hospital Brno, Czech Republic; Katja Weisel, Universitätsklinikum Hamburg-Eppendorf; Michele Cavo, Università di Bologna; Jacob P. Laubach, Harvard Medical School; Gordon Cook, University of Leeds; Shinsuke Iida, Nagoya City University; Lotfi Benboubker, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire (CHRU), Tours, France; Saad Z. Usmani, Levine Cancer Institute; Sung-Soo Yoon, Seoul National University; Nizar J. Bahlis, University of Calgary; Christoper Chiu, Janssen Research and Development, LLC, Spring House, PA, USA; Jon Ukropec, Janssen Global Medical Affairs, Horsham, PA, USA; Jordan M. Schecter, Janssen Research & Development, LLC, Raritan, NJ, USA; Xiang Qin, Janssen Research and Development, LLC, Spring House, PA, USA; Lisa O'Rourke, Janssen Research and Development, LLC, Spring House, PA, USA; Meletios A. Dimopoulos, National and Kapodistrian University of Athens
• Language: English
• Date: 2020-01-31
• Publisher: The Ferrata-Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the Ferrata Storti Foundation
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2019.217448
• Title of Journal or Parent Work: Haematologica
• Volume: 105
• Issue: 2
• Start Page: 468
• End Page: 477
• Grant/Funding Information: These studies (ClinicalTrials.gov Identifiers: NCT02076009 and NCT02136134) were sponsored by Janssen Research & Development, LLC.; Editorial and medical writing support were provided by Kristin Runkle, PhD, of MedErgy, and were funded by Janssen Global Services, LLC.
• Keywords: Dexamethasone; Lenalidomide; Bortezomib; Humans; Antibodies, Monoclonal; Multiple Myeloma; Aged; Antineoplastic Combined Chemotherapy Protocols
• Research Categories: Biology, Cell; Health Sciences, Oncology; Health Sciences, Immunology

Abstract

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/lenalidomide/ dexamethasone prolonged progression-free survival versus lenalidomide/ 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 treatmentemergent adverse event (daratumumab: 45.0%; control: 37.1%). Infusionrelated 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.