Adding daratumumab to carfilzomib/dexamethasone prolongs PFS and OS in R/R MM

In the open-label randomised phase 3 CANDOR trial, the addition of anti-CD38 antibody daratumumab to carfilzomib and dexamethasone reduced the risk of disease progression or death by 37% compared with carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma (MM).

Prof. Saad Z. Usmani (UNC-Chapel Hill School of Medicine, USA) presented the initial results of the trial, which randomised 466 patients (2:1 ratio) with relapsed/refractory MM previously treated with 1 to 3 prior therapies to either daratumumab + carfilzomib/dexamethasone (n=312) or carfilzomib/dexamethasone alone (n=154) [1]. The primary endpoint of this study was progression-free survival (PFS). Key secondary endpoints were overall response rate, minimal residual disease-negative status, complete response rate at 12 months, overall survival (OS), duration of response, and safety.

The median PFS was not yet reached at median follow-up of 15.8 months, but the PFS was significantly improved with the addition of daratumumab versus carfilzomib/dexamethasone alone (HR 0.63; 95% CI 0.46-0.85; P=0.0014). The median OS had not yet been reached in either arm at a median follow-up of 17 months (HR 0.75; 95% CI 0.49-1.13; P=0.08). The overall response rate was 84.3% with daratumumab + carfilzomib/dexamethasone compared with 74.7% with only carfilzomib/dexamethasone (P=0.0040). Complete response was observed in 28.5% of the daratumumab + carfilzomib/dexamethasone arm versus 10.4% in the carfilzomib/dexamethasone arm. At 12 months, the minimal residual disease-negative rate was 12.5% for patients receiving daratumumab + carfilzomib/dexamethasone versus a mere 1.3% patients treated with carfilzomib/dexamethasone alone.

The safety profile was similar to what has been previously reported for each individual medicine. Grade ≥3 adverse events were reported in 56.2% (daratumumab + carfilzomib/dexamethasone¬) versus 45.8% patients (carfilzomib/dexamethasone). Treatment discontinuation rates due
to adverse events were similar in both arms (22.4% vs 24.8%, respectively). In the daratumumab + carfilzomib/dexamethasone arm, 5 treatment-related deaths occurred as compared with no deaths in the control arm; all were due to infections. Myeloma patients taking daratumumab are known to be at higher risk for infections attributable to reduced cellular immunity.

In conclusion, the CANDOR trial results showed deep and durable responses by adding daratumumab to carfilzomib/dexamethasone in relapsed/refractory MM patients, and the safety profile was consistent with previous experience.

1. Usmani SZ, et al. LBA-6, ASH 2019, 7-10 December, Orlando, USA.