Carfilzomib, dexamethasone and daratumumab versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (CANDOR): updated results from a randomized, multicenter, open-label phase 3 study

Background

Despite recent advances in treatment options, there remains an unmet need for treatment of patients with relapsed or refractory multiple myeloma, particularly in those previously exposed or refractory to lenalidomide. This updated CANDOR phase 3 efficacy and safety analysis compared carfilzomib, daratumumab and dexamethasone (KdD) with carfilzomib and dexamethasone (Kd) in patients with myeloma multiple relapsed or refractory.

Methods

In this updated review of the CANDOR, randomized, multicenter, open-label, phase 3 study, patients (aged ≥18 years) with relapsed or refractory multiple myeloma, at least a partial response to between a and three previous treatments, and Eastern Cooperative Oncology A group performance status of 0 to 2, were recruited from 102 medical centers around the world and assigned at random (2: 1) by interactive voice response software or web to receive KdD or Kd. Participants were stratified by disease stage, previous exposure to a proteasome inhibitor or anti-CD38 antibody, and number of prior therapies. All patients received intravenous infusions of carfilzomib twice weekly at 56 mg / m2 (20 mg / m2 on days 1 and 2 during cycle 1) on days 1, 2, 8, 9, 15 and 16 of each 28-day cycle. Daratumumab (8 mg / kg) was administered intravenously on days 1 and 2 of cycle 1 and at 16 mg / kg per week for the remaining doses of the first two cycles, then every 2 weeks for four cycles (cycles 3 to 6), and every 4 weeks thereafter. Patients received 40 mg of dexamethasone per week (20 mg for patients over 75 years old). This analysis was a planned interim analysis for overall survival; however, at the time of data cutoff, overall survival data was not mature. The primary endpoint was progression-free survival. Here, we provide updated progression-free survival data, centrally assessed by Onyx Response Computer Algorithm in the intention-to-treat population, with an additional 11-month follow-up. Adverse events were assessed in the safety population, which included all participants who received at least one dose of trial treatment. CANDOR is registered with ClinicalTrials.gov, NCT03158688, and is active but not recruiting.

Results

Between June 13, 2017 and June 25, 2018, 466 patients were included, of which 312 received KdD and 154 received Kd. At the data cut-off date (June 15, 2020), the median follow-up was 27.8 months (IQR 25.6–29.5) for KdD and 27.0 months (13.2–28.6) for Kd . The median progression-free survival was 28.6 months (95% CI 22.7 – not estimable [NE]) in the KdD group and 15.2 months (11.1–19.9) in the Kd group (hazard ratio 0.59 [95% CI 0·45–0·78], log-rank p vs 25 [16%], respectively), hypertension (65 [21%] vs 23 [15%]), pneumonia (54 [18%] vs 14 [9%]) and anemia (53 [17%] vs 23 [15%]). Serious adverse events occurred in 194 (63%) patients with KdD and 76 (50%) patients with Kd. Adverse events leading to death occurred in 27 (9%) patients in the KdD group and seven (5%) in the Kd group; most often septic shock (five [2%] vs one (1%]) and pneumonia (four [1%] vs nothing). No new treatment-related deaths have occurred since the primary analysis.

Interpretation

A clear and sustained progression-free survival advantage of KdD over Kd with longer follow-up was confirmed, making KdD an emerging standard of care for patients with relapsed or refractory multiple myeloma.

Funding

Amgen and Janssen.

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About Jonathan J. Kramer

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