Results from the phase 3 CANDOR trial show that for relapsed/refractory multiple myeloma, adding daratumumab (D) to carfilzomib/dexamethasone (Kd) increases efficacy compared with Kd alone.
"Lenalidomide and bortezomib frontline exposure has raised a growing need for novel treatments for patients with relapsed or refractory multiple myeloma," write the study investigators in their publication in The Lancet, led by Meletios Dimopoulos, MD, Professor and Chairman of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece. For patients with relapsed or refractory disease, KdD displayed substantial promise in terms of efficacy and safety in a previous phase 1 trial.
For the open-label phase 3 trial, 466 patients with relapsed/refractory multiple myeloma, recruited from 102 sites across North America, Europe, Australia, and Asia, were randomized 2:1 to receive KdD or Kd. All patients received carfilzomib at a dosage of 20 mg/m2 on Days 1 and 2 of Cycle 1 followed by 56 mg/m2 twice weekly, along with dexamethasone 40 mg weekly, or 20 mg for patients aged 75 years or older starting in the second week. Patients in the daratumumab arm also received daratumumab 8 mg/kg administered intravenously on Days 1 and 2 of Cycle 1 and then 16 mg/kg weekly for the remaining doses of the first two cycles, followed by every two weeks for Cycles 3 to 6 and every four weeks thereafter. The trial's primary end point was progression-free survival in the intention-to-treat population.
At a median follow-up of approximately 17 months, KdD prolonged median progression-free survival compared with Kd (not reached vs 15.8 months), with a longer median duration of treatment (70.1 vs 40.3 weeks). The KdD arm experienced a somewhat higher rate of grade 3 or higher adverse events (82% vs 74%), although the rates of adverse events leading to treatment discontinuation were similar between arms (22% vs 25%).
"KdD significantly prolonged progression-free survival versus Kd in patients with relapsed or refractory multiple myeloma and was associated with a favorable benefit–risk profile," conclude Dr. Dimopoulos and colleagues.
For More Information
Dimopoulos M, Quach H, Mateos MV, et al (2020). Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet, 396(10245):186-197. DOI:10.1016/S0140-6736(20)30734-0
Image credit: Michaela Reagan. Courtesy of the National Cancer Institute / Dana-Farber Harvard Cancer Center