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

Andrew Spencer, Suzanne Lentzsch, Katja Weisel, Hervé Avet-Loiseau, Tomer M Mark, Ivan Spicka, Tamas Masszi, Birgitta Lauri, Mark-David Levin, Alberto Bosi, Vania Hungria, Michele Cavo, Je-Jung Lee, Ajay K Nooka, Hang Quach, Cindy Lee, Wolney Barreto, Paolo Corradini, Chang-Ki Min, Emma C ScottAsher A Chanan-Khan, Noemi Horvath, Marcelo Capra, Meral Beksac, Roberto Ovilla, Jae-Cheol Jo, Ho-Jin Shin, Pieter Sonneveld, David Soong, Tineke Casneuf, Christopher Chiu, Himal Amin, Ming Qi, Piruntha Thiyagarajah, A Kate Sasser, Jordan M Schecter, Maria-Victoria Mateos

Research output: Contribution to journalArticlepeer-review

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 to 27.7) months of median follow-up, daratumumab plus bortezomib and dexamethasone prolonged progression-free survival (median: 16.7 versus 7.1 months; hazard ratio, 0.31; 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.

TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT02136134.

Original languageEnglish
JournalHaematologica
DOIs
Publication statusE-pub ahead of print - Sep 20 2018

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