CASTOR Trial Shows Triplet Improves OS Over Doublet in R/R MM

Adding daratumumab to bortezomib and dexamethasone significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (MM), according to final analysis of the CASTOR trial.

A multinational research team led by Pieter Sonneveld, MD, PhD, of Erasmus MC Cancer Institute in Rotterdam, Netherlands, found that patients who also received daratumumab had significantly lower risk of death and significantly longer median OS than those who received only bortezomib and dexamethasone.

“To our knowledge, our results, together with the OS benefit observed with daratumumab plus lenalidomide and dexamethasone in the phase III POLLUX study, demonstrate for the first time an OS benefit with daratumumab-containing regimens in [relapsed or refractory MM],” the authors wrote in an article published in the Journal of Clinical Oncology.

In the multicenter, phase III CASTOR study, patients who had received at least one line of prior therapy were randomly assigned to receive bortezomib and dexamethasone for up to eight cycles with or without daratumumab until disease progression. After disease progression, patients receiving bortezomib and dexamethasone were offered daratumumab monotherapy.

The primary analysis of CASTOR showed a progression-free survival benefit for the triplet over the doublet with a median follow-up of 7.2 months. In their study, Dr. Sonneveld and colleagues performed a final analysis to update efficacy and safety results.

Compared with patients who received bortezomib and dexamethasone alone, those who received daratumumab, bortezomib, and dexamethasone had a “significant OS benefit” at a median follow up of 72.6 months (hazard ratio, 0.74; 95% CI, 0.59-0.92; P=.0075). In addition, patients who received the triplet treatment had a median OS of 49.6 months, compared with 38.5 months for patients who received the doublet.

Patients aged 65 years or older and those who received one or two prior lines of therapy showed a significantly longer OS with the triplet. That benefit was also achieved in those with International Staging System stage III disease, high-risk cytogenetic abnormalities, and prior bortezomib treatment.

“Treatment of patients with [relapsed or refractory MM] with [daratumumab with bortezomib and dexamethasone] results in a significant reduction in the risk of death compared with [bortezomib and dexamethasone] alone, with the greatest OS benefit observed in patients who received one prior line of therapy,” the researchers wrote. “These results provide strong rationale for early use of daratumumab to maximize patient benefit.”

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. 2023;41(8):1600-1609. doi:10.1200/JCO.21.02734