Adding daratumumab to bortezomib and dexamethasone improved progression-free survival, overall response rate, and time to next treatment compared with bortezomib and dexamethasone alone among patients with relapsed or refractory multiple myeloma, according to an interim analysis presented at European Society for Medical Oncology (ESMO) 2016 Congress.1
Daratumumab is a human CD38-directed monoclonal antibody approved by the U.S. Food and Drug Administration as a single agent for heavily pretreated multiple myeloma. In the CASTOR study (ClinicalTrials.gov Identifier: NCT02136134), researchers evaluated the efficacy and safety of daratumumab in combination with bortezomib and dexamethasone.
Investigators enrolled 498 patients with multiple myeloma who had received at least 1 prior line of therapy. Of those, 76% had received prior treatment with an immunomodulatory agent, 66% had previously received bortezomib, and 48% had received both. Thirty-three percent were refractory to immunomodulatory treatment and 32% were refractory to the last line of therapy.
Participants were randomly assigned 1:1 to receive 8 cycles of bortezomib and dexamethasone with or without daratumumab until disease progression or unacceptable toxicity.
At a median follow-up of 7.4 months, results showed that daratumumab significantly reduced the risk of progression by 61% compared with bortezomib and dexamethasone alone (hazard ratio [HR], 0.39; 95% CI, 0.28-0.53; P < .0001).
The overall response rate was 83% with daratumumab versus 63% without (P < .0001), with 19% and 9% achieving complete responses or better (P = .0012). Daratumumab was associated with a 70% reduction in the time to next therapy compared with bortezomib and dexamethasone alone (HR, 0.30; 95% CI, 0.20-0.45; P < .0001).
Median overall survival was not yet reached for either treatment arm.
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The safety profile of daratumumab, bortezomib, and dexamethasone is consistent with previous reports.
The findings suggest that this novel combination should be considered a new standard of care for patients with relapsed or refractory multiple myeloma receiving bortezomib and dexamethasone.
- Weisel K, Palumbo A, Chanan-Khan A, et al. Phase 3 randomised study of daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM): CASTOR. Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.