Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR

• Authors: Andrew Spencer, Monash University; Suzanne Lentzsch, Columbia University; Katja Weisel, Eberhard Karls University of Tubingen; Herve Avet-Loiseau, CHU Rangueil; Tomer M. Mark, University of Colorado; Ivan Spicka, Charles University Prague; Tamas Masszi, Semmelweis University; Birgitta Lauri, Sunderbyn Hospital; Mark-David Levin, Albert Schweitzer Hospital; Alberto Bosi, Careggi Hospital; Vania Hungria, Irmandade Santa Casa De Misericordia Sao Paulo; Michele Cavo, University of Bologna; Je-Jung Lee, Chonnam National University; Ajay Nooka, Emory University; Hang Quach, University of Melbourne; Cindy Lee, Royal Adelaide Hospital; Wolney Barreto, Hospital of Santa Marcelina; Paolo Corradini, University of Milan; Chang-Ki Min, Seoul St Marys Hospital; Emma C. Scott, Oregon Health and Science University; Asher A. Chanan-Khan, Mayo Clinic Florida; Noemi Horvath, Royal Adelaide Hospital; Marcelo Capra, Hospital Mae de Deus; Meral Beksac, Ankara University; Roberto Ovilla, Hospital Angeles Lomas; Jae-Cheol Jo, Ulsan University Hospital; Ho-Jin Shin, Pusan National University; Pieter Sonneveld, Erasmus Medical Center; David Soong, Janssen Research & Development, LLC; Tineke Casneuf, Janssen Research & Development, LLC; Christopher Chiu, Janssen Research & Development, LLC; Himal Amin, Janssen Research & Development, LLC; Ming Qi, Janssen Research & Development, LLC; Piruntha Thiyagarajah, Janssen Research & Development, LLC; A. Kate Sasser, Genmab US Inc; Jordan M. Schecter, Janssen Research & Development, LLC; Maria-Victoria Mateos, University Hospital of Salamanca
• Journal Title: Haematologica
• Volume: Volume 103, Number 12
• Publisher: Ferrata Storti Foundation | 2018-11-30, Pages 2079-2087
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3324/haematol.2018.194118
• Subjects: Health Sciences, Oncology; Chemistry, Pharmaceutical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; MINIMAL RESIDUAL DISEASE; LOW-DOSE DEXAMETHASONE; OPEN-LABEL; INTERGROUPE FRANCOPHONE; ANTIBODY DARATUMUMAB; TARGETING CD38; LENALIDOMIDE; POMALIDOMIDE; SURVIVAL; THERAPY

Abstract

Daratumumab, a CD38 human monoclonal antibody, demonstrated significant clinical activity in combination with bortezomib and dexamethasone versus bortezomib and dexamethasone alone in the primary analysis of CASTOR, a phase 3 study in relapsed and/or refractory multiple myeloma. A post hoc analysis based on treatment history and longer follow up is presented. After 19.4 (range: 0-27.7) months of median follow up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; ha zard ra ti o, 0.3 1; 95% confidence interval, 0.24 -0.39; P<0.0001) and improved the overall response rate (83.8% versus 63.2%; P<0.0001) compared with bortezomib and dexamethasone alone. The progression-free survival benefit of daratumumab plus bortezomib and dexamethasone was most apparent in patients with 1 prior line of therapy (median: not reached versus 7.9 months; hazard ratio, 0.19; 95% confidence interval, 0.12-0.29; P<0.0001). Daratumumab plus bortezomib and dexamethasone was also superior to bortezomib and dexamethasone alone in subgroups based on prior treatment exposure (bortezomib, thalidomide, or lenalidomide), lenalidomide-refractory status, time since last therapy (≤12, >12, ≤6, or >6 months), or cytogenetic risk. Minimal residual disease–negative rates were >2.5-fold higher with daratumumab across subgroups. The safety profile of daratumumab plus bortezomib and dexamethasone remained consistent with longer follow up. Daratumumab plus bortezomib and dexamethasone demonstrated significant clinical activity across clinically relevant subgroups and provided the greatest benefit to patients treated at first relapse.