As reported in The Lancet by Meletios Dimopoulos, MD, and colleagues, the phase III CANDOR trial has shown prolonged progression-free survival with carfilzomib, dexamethasone, and daratumumab (KdD) vs carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma.

Meletios Dimopoulos, MD

Study Details

In the open-label trial, 466 patients from sites in North America, Europe, Australia, and Asia were randomly assigned 2:1 between June 2017 and June 2018 to receive KdD (n = 312) or Kd (n = 154). Treatment in 28-day cycles was continued until disease progression or unacceptable toxicity. All patients received twice weekly carfilzomib at 56 mg/m² after receiving 20 mg/m² on days 1 and 2 during cycle 1. Daratumumab was given at 8 mg/kg on days 1 and 2 of cycle 1 and at 16 mg/kg weekly for the remaining doses of the first 2 cycles, then every 2 weeks for 4 cycles, and every 4 weeks thereafter. Patients received 40 mg of dexamethasone weekly. The primary endpoint was progression-free survival as assessed by independent review committee in the intention-to-treat population.

Progression-Free Survival

Median follow-up for progression-free survival was 16.9 months in the KdD group and 16.3 months in the Kd group.

Median progression-free survival was not reached in the KdD group (95% confidence interval [CI] = not estimable) vs 15.8 months (95% CI = 12.1 months–not estimable) in the Kd group (hazard ratio [HR] = 0.63, 95% CI = 0.46–0.85, P = .0027). Rates at 18 months were 62% vs 43%. Median progression-free survival was not reached vs 12.1 months (HR = 0.529, 95% CI = 0.342–0.818) among patients previously treated with lenalidomide, and was not reached vs 11.1 months (HR = 0.474, 95% CI = 0.288–0.781) among those who were refractory to lenalidomide treatment.

Overall response rates were 84% vs 75% (odds ratio = 1.925, P = .0080), with very good partial response or better in 69% vs 49% and compete response in 29% vs 10%. Median time to first response was 1 month in both groups. At a median follow-up of approximately 17.2 months, median overall survival had not been reached in either the KdD group or Kd group; at data cutoff, death had occurred in 19% vs 23% of patients (HR = 0.75, P = .17). Kaplan-Meier estimated 18-month overall survival rates were 80% vs 74%.

Adverse Events

Median treatment duration was 70.1 weeks in the KdD group and 40.3 weeks in the Kd group. Grade ≥ 3 adverse events were reported in 82% of patients in the KdD group and in 74% of patients in the Kd group. Grade ≥ 3 adverse events in the KdD group included thrombocytopenia (24%, vs 16% in the Kd group), hypertension (18% vs 13%), neutropenia (9% vs 6%), anemia (17% vs 15%), fatigue (7% vs 5%), pneumonia (13% vs 9%), and diarrhea (4% vs 1%). Serious adverse events occurred in 56% vs 46% of patients. Adverse events led to treatment discontinuation in 22% vs 25%. Adverse events led to death in 30 patients (10%) in the KdD group vs 8 patients (5%) in the Kd group. Five deaths—all in the KdD group—were considered treatment-related, with causes consisting of pneumonia, sepsis with development of Clostridium difficile enterocolitis, septic shock in the setting of pneumocystis pneumonia, acinetobacter infection, and cardiorespiratory arrest.

The investigators concluded, “KdD significantly prolonged progression-free survival vs Kd in patients with relapsed or refractory multiple myeloma and was associated with a favorable benefit-risk profile.”

Saad Z. Usmani, MD, of Atrium Health, Charlotte, North Carolina, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Amgen. For full disclosures of the study authors, visit thelancet.com.