The following is a summary of “Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial,” published in the March 2023 issue of Oncology by Sonneveld, et al.

For a study, researchers sought to report updated efficacy and safety results at the final analysis for overall survival (OS) in the CASTOR trial.

CASTOR was a phase III clinical trial conducted at multiple medical centers that randomly assigned patients with relapsed or refractory multiple myeloma (RRMM) and at least one prior line of therapy to receive bortezomib and dexamethasone with or without daratumumab. Patients who received only bortezomib and dexamethasone were allowed to receive daratumumab monotherapy after disease progression following a positive primary analysis and a protocol amendment.

After a median follow-up of 72.6 months (0.0 to 79.8 months), daratumumab plus bortezomib and dexamethasone (D-Vd) showed a significant benefit in overall survival (OS) compared to bortezomib and dexamethasone (Vd) alone, with a hazard ratio of 0.74 and 95% CI from 0.59 to 0.92 (P = .0075). The median OS for patients treated with D-Vd was 49.6 months, while 38.5 months for those treated with Vd. The results of prespecified subgroup analyses also showed that D-Vd was beneficial for most subgroups, including patients who were ≥65 years or older, patients who had received one or two lines of therapy before the study, those with International Staging System stage III disease, those with high-risk cytogenetic abnormalities, and those who had received bortezomib treatment before. The most common grade 3/4 treatment-emergent adverse events with D-Vd were thrombocytopenia (46.1% vs. 32.9%), anemia (16.0% vs. 16.0%), neutropenia (13.6% vs. 4.6%), lymphopenia (10.3% vs. 2.5%), and pneumonia (10.7% vs. 10.1%), with each occurring in ≥10% of patients.

Daratumumab plus bortezomib and dexamethasone significantly prolonged OS in patients with relapsed or refractory multiple myeloma, with the greatest OS benefit observed in patients with one prior line of therapy. The study, together with the OS benefit observed with daratumumab plus lenalidomide and dexamethasone in the phase III POLLUX study, demonstrated for the first time an OS benefit with daratumumab-containing regimens in RRMM.

Reference: ascopubs.org/doi/full/10.1200/JCO.21.02734