Data from a subgroup analysis of CANDOR supported the efficacy of daratumumab plus carfilzomib and dexamethasone in RRMM, even in high-risk patients.
CANDOR is a multicenter, phase 3, randomized trial that compared the efficacy and safety of carfilzomib with dexamethasone and daratumumab (KdD) to that of carfilzomib plus dexamethasone (Kd) in adults with relapsed/refractory multiple myeloma (RRMM). KdD demonstrated superior efficacy and a deeper response compared to Kd with a hazard ratio of 0.63 (P = .0027). These benefits were maintained after an additional 11 months, with a median progression-free survival (PFS) of 28.6 months with KdD versus 15.2 months with Kd alone. In a 2022 publication, Ola Landgren and colleagues reported findings from a subgroup analysis that evaluated outcomes based on cytogenetic risk.
A total of 466 patients with RRMM were randomized to KdD (n = 312) or Kd alone (n = 154). Overall, baseline demographics and disease characteristics were well balanced between the 2 groups. A total of 247 (79.2%) patients in the KdD group and 135 (87.7%) patients in the Kd group had valid cytogenetic results. In the KdD and Kd groups, 22.1% and 23.4%, respectively, had high-risk cytogenetics, with del(17p13) being the most common aberration. More than half of the patients were classified as standard risk in each cohort, 57.1% KdD and 64.3% Kd.
Overall response rate (ORR) was higher in the KdD group versus the Kd group, regardless of cytogenetic risk group: 81.2% versus 55.6% in high-risk patients and 86.5% versus 78.8% in standard-risk patients. Similar results were seen in patients with prior lenalidomide exposure, with an ORR of 84.6% with KdD versus 66.7% with Kd in high-risk patients and 79.2% versus 73.1% in standard-risk patients. In patients with prior bortezomib exposure, the ORR was 80.6% with KdD and 55.9% with Kd in high-risk patients and 85.8% with KdD and 76.7% with Kd in standard-risk patients. For all risk groups, PFS favored KdD over Kd. For patients with high-risk cytogenetics, the median PFS with KdD was 11.2 months versus 7.4 months with Kd, while the median PFS in standard-risk patients was not reached with KdD and 16.6 months with Kd.
These results support the findings from CANDOR and show improved responses with the addition of daratumumab. Although this study may be limited by small patient numbers in some subgroups, as well as 84 patients with unknown cytogenetic risk, this analysis supports the use of KdD in RRMM patients, regardless of cytogenetic risk.
Reference
- Landgren O, Weisel K, Rosinol R, et al. Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study. Br J Haematol. 2022;198:988-993.
