Combination Regimen Prolongs Overall Survival in Relapsed/Refractory Multiple Myeloma

Daratumumab, bortezomib, and dexamethasone (D-Vd) significantly prolonged overall survival in patients with relapsed or refractory multiple myeloma, according to updated efficacy results of the phase III CASTOR study published in the Journal of Clinical Oncology.

“To our knowledge, our results, together with the overall survival benefit observed with daratumumab plus lenalidomide and dexamethasone in the phase III POLLUX study, demonstrate for the first time an overall survival benefit with daratumumab-containing regimens in relapsed or refractory multiple myeloma,” researchers wrote.

The open-label CASTOR trial randomly assigned patients up to eight cycles of bortezomib and dexamethasone (Vd), with or without daratumumab, until disease progression. After a primary analysis revealed prolonged progression-free survival with D-Vd, patients receiving Vd were offered daratumumab monotherapy after disease progression.

The updated final analysis showed that after a median follow-up of 72.6 months, median overall survival was 49.6 months with D-Vd  compared with 38.5 months with Vd. Researchers reported a 26% reduction in the risk of death with D-Vd versus Vd alone.

Prespecified subgroup analyses showed the greatest benefit among patients with one prior line of therapy. Nevertheless, D-Vd improved overall survival across most subgroups, including patients 65 years and older, patients with two prior lines of therapy, patients with International Staging System stage III disease, patients with high-risk cytogenetic abnormalities, and patients with prior bortezomib treatment.

The most common grade 3/4 treatment-emergent adverse events with D-Vd were thrombocytopenia (46.1%), anemia (16.0%), neutropenia (13.6%), lymphopenia (10.3%), and pneumonia (10.7%).

“These results provide strong rationale for early use of daratumumab to maximize patient benefit,” researchers concluded.

Janssen Research & Development supported the study.

Reference:
Sonneveld P, Chanan-Khan A, Weisel K, et al. Overall survival with daratumumab, bortezomib, and dexamethasone in previously treated multiple myeloma (CASTOR): a randomized, open-label, phase III trial. J Clin Oncol. Published online November 22, 2022. doi:10.1200/JCO.21.02734