Carfilzomib, Dexamethasone & Daratumumab for Patients With RRMM
By Sarah LaCorte
ORLANDO— Results from the primary analysis of the phase II CANDOR study evaluating carfilzomib in combination with dexamethasone and daratumumab (KdD) compared to carfilzomib and dexamethasone alone (Kd) in patients with relapsed or refractory multiple myeloma were presented in a late-breaking abstract session at the 2019 ASH Annual Meeting (Blood 2019; doi.org/10.1182/blood-2019-132629).
At a median follow-up of 17 months, the study met its primary endpoint of progression-free survival (PFS), resulting in a 37 percent reduction in the risk of disease progression or death in patients receiving KdD (HR=0.63; 95% CI: 0.464, 0.854; p=0.0014). Median PFS was not reached for the KdD arm versus 15.8 months for the Kd arm.
In addition to meeting the primary endpoint, the KdD combination demonstrated efficacy in key secondary endpoints, including overall response rate (ORR), minimal residual disease (MRD) negative-complete response at 12 months, and overall survival (OS). The ORR was 84.3 percent versus 74.7 percent (p=0.0040), and the rate of complete response or better was 28.5 percent versus 10.4 percent for the KdD and Kd arms, respectively. The analysis found the MRD-negative complete response rate at 12 months was 12.5 percent for KdD versus 1.3 percent for Kd (p<0.0001), a nearly 10-times higher response rate versus Kd-treated patients. The median OS was not reached in either group (HR=0.75; 95 percent CI: 0.49, 1.13; p=0.08).
"With the increasing use of frontline lenalidomide based therapies, there is an emerging need for lenalidomide-sparing regimens at relapse," said Saad Usmani, MD, Chief of the Plasma Cell Disorders Division and Director of Clinical Research in Hematologic Malignancies, Atrium Health's Levine Cancer Institute. "The CANDOR trial demonstrates the potential efficacy of a lenalidomide-sparing regimen that combines two effective targeted agents and provides deep and durable responses upon relapse."
The safety of KdD was consistent with the known safety profiles of the individual agents. The most frequently reported (≥ 20% of subjects in either treatment arm [KdD, Kd]) treatment emergent adverse events included thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue, and dyspnea. The incidence of treatment emergent grade 3 or higher, serious, and fatal adverse events was higher in the KdD arm compared to the Kd arm. The rate of treatment discontinuation due to AEs was similar in both arms. Additional efficacy endpoints and key subgroup analyses will be presented at future meetings.