At the 2019 American Society for Hematology (ASH) Annual Meeting, Saad Usmani, MD, MBBS (Atrium Health, Charlotte, North Carolina, United States), presented results from the randomized phase III CANDOR trial, evaluating the combination of carfilzomib, dexamethasone, and daratumumab (KdD) for treatment of patients with relapsed/refractory multiple myeloma (Abstract LBA6). Patients (N = 466) who had progressed on one to three prior therapies received treatment with either KdD or carfilzomib and dexamethasone alone (Kd). Prior treatment with carfilzomib or an anti-CD38 antibody was allowed.
Addition of daratumumab to carfilzomib and dexamethasone resulted in a significant improvement in progression-free survival (PFS). The median PFS was not reached in patients receiving KdD, compared to 15.8 months in patients receiving Kd (HR 0.63, P = .0014). The PFS benefit of KdD was consistent regardless of prior lenalidomide exposure and in patients who were considered lenalidomide refractory. The overall response rate (ORR) was 84.3% and 74.7% in the KdD and Kd groups, respectively (P = .0040). Significantly more patients in the KdD group had achieved minimal residual disease (MRD) negative complete response (CR) at 12 months compared to the Kd group (12.5% vs 1.3%; P<.0001). At a median follow-up of 17 months, the median overall survival (OS) had not yet been reached in either treatment arm, though there was a trend in favor of KdD (HR 0.75, P = .08).
The safety profile of KdD was consistent with the known safety profile of the individual treamtents. A total of 82.1% of patients in the KdD group experienced grade 3 or higher adverse events (AEs), compared to 73.9% in the Kd group. Despite the increase in AEs among patients receiving KdD, rates of treatment discontinuation due to AEs were similar in the two treatment groups (22.4% vs 24.8%).
Dr Usmani concluded that the combination of KdD significantly improves PFS compared to Kd alone, resulting in deeper responses and a 10-fold increase in MRD negativity with a tolerable safety profile. Importantly, this combination provides an immunomodulatory drug (IMiD)-free treatment option that can be used in patients who are resistant to IMiD treatment following upfront lenalidomide. Dr Usmani indicated that KdD should be considered a new standard of care in relapsed/refractory multiple myeloma, particularly in patients with lenalidomide-resistant disease.
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