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

作者：Spencer, Andrew^*; Lentzsch, Suzanne; Weisel, Katja; Avet-Loiseau, Herve; Mark, Tomer M.; Spicka, Ivan; Masszi, Tamas; Lauri, Birgitta; Levin, Mark-David; Bosi, Alberto; Hungria, Vania; Cavo, Michele; Lee, Je-Jung; Nooka, Ajay K.; Quach, Hang; Lee, Cindy; Barreto, Wolney; Corradini, Paolo; Min, Chang-Ki; Scott, Emma C.; Chanan-Khan, Asher A.; Horvath, Noemi; Capra, Marcelo; Beksac, Meral; Ovilla, Roberto; Jo, Jae-Cheol; Shin, Ho-Jin; Sonneveld, Pieter; Soong, David; Casneuf, Tineke

来源：Haematologica-The Hematology Journal, 2018, 103(12): 2079-2087.

DOI：10.3324/haematol.2018.194118

• MINIMAL RESIDUAL DISEASE
• LOW-DOSE DEXAMETHASONE
• OPEN-LABEL
• INTERGROUPE FRANCOPHONE
• ANTIBODY DARATUMUMAB
• TARGETING CD38
• LENALIDOMIDE
• POMALIDOMIDE
• SURVIVAL
• THERAPY

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 EGISTRATION: clinicaltrials.gov identifier: NCT02136134.

• 出版日期2018-11-30