OBJECTIVES: We applied indirect treatment comparison to compare progression-free survival (PFS) and overall survival (OS) between carfilzomib, dexamethasone, and daratumumab (KdD) and carfilzomib, lenalidomide, and dexamethasone (KRd) among patients with relapsed and/or refractory multiple myeloma (R/RMM), given the lack of head-to-head trials comparing the two regimens. The lenalidomide-exposed (len-exposed) subgroup was investigated, considering the increased use of len in R/RMM.

METHODS: Data from CANDOR (KdD; N = 292 [Intention to treat, ITT]; N = 112 [len-exposed]) and ASPIRE (KRd; N = 386 [ITT]; N = 77 [len-exposed]) trials were used. PFS and OS of KdD vs. KRd were performed in both the ITT population as well as the len-exposed subgroup, adjusting for differences in patient characteristics, such as performance status, clinical characteristics, and prior treatments. Additionally, time-varying hazard models were assessed before and after 18 cycles (28-day cycle) in the ITT population, as carfilzomib was discontinued after cycle 18 in the KRd arm.

RESULTS: In the ITT after weighting, PFS and OS of KdD vs KRd were comparable (PFS hazard ratio [HR], 95% confidence internal [CI]: 0.98 [0.72, 1.24]; OS HR: 0.94 [0.68, 1.19]). PFS and OS of KdD vs. KRd were comparable before cycle 18 (PFS HR: 1.20 [0.70, 1.70]; OS HR: 1.36 [0.80, 1.92]); the results trended towards improvement in PFS and OS of KdD after cycle 18, though the HRs were not statistically significant (PFS HR: 0.74 [0.46, 1.01]; OS HR: 0.77 [0.48, 1.06]). In the len-exposed subgroup after weighting, PFS and OS of KdD vs. KRd were comparable (PFS HR: 1.01 [0.38, 1.64]; OS HR: 1.11 [0.47, 1.75]).

CONCLUSIONS: In a mixed population with the majority being len-naïve, KdD and KRd are equally effective. There is a trend towards a more favorable long-term OS benefit in KdD vs KRd in the ITT and after cycle 18.