Patients with relapsed or refractory multiple myeloma (RRMM) had significantly prolonged survival with the three-drug combination of daratumumab, bortezomib, and dexamethasone (D-Vd) compared with bortezomib plus dexamethasone (Vd) alone, according to results from the CASTOR trial.
CASTOR was a phase III trial that enrolled 498 patients with RRMM who had treatment with at least one prior line of therapy. Patients were randomly assigned to up to 8 cycles of Vd with or without daratumumab.
With a median follow-up of 72.6 months, there was a 26% reduction in the risk for death in patients treated with D-Vd (hazard ratio [HR]=0.74; 95% CI, 0.59-0.92; P=.0075). Median overall survival was 49.6 months for D-Vd compared with 38.5 months for Vd alone.
“For the first time to our knowledge, the combination of daratumumab and a standard-of-care regimen significantly improved overall survival in patients with RRMM,” study researchers wrote.
The researchers noted a particular overall survival benefit was seen in patients with one prior line of therapy (HR=0.56; 95% CI, 0.39-0.80). The overall survival benefit was observed across most patient subgroups, including those aged 65 years or older and those with poor prognosis.
D-Vd was also associated with significantly higher rates of MRD-negativity (15.1% vs. 1.6%; P<.0001), which was associated with improved overall survival.
“It appears that the superiority in overall survival is derived from patients who achieved MRD negativity in the D-Vd group because overall survival was similar in the D-Vd and Vd groups in patients who were MRD-positive,” the researchers wrote.
After disease progression, the median time to crossover to daratumumab for patients in the Vd arm was 20.5 months. Of the patients who crossed over, the median overall survival is 63.4 months.
The most common grade 3/4 treatment-emergent adverse events with D-Vd compared with 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%).
The researchers concluded that “these results provide strong rationale for early use of daratumumab to maximize patient benefit.”
Source: 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. 2022;doi: 10.1200/JCO.21.02734