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Carfilzomib plus Dexamethasone and Daratumumab versus Carfilzomib plus Dexamethasone: Subgroup Analysis of the CANDOR Study Focuses on Cytogenetic Risk

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CANDOR is a multicenter, phase 3, randomized trial that compared the efficacy and safety of carfilzomib with dexamethasone and daratumumab (KdD) to carfilzomib plus dexamethasone (Kd) in adults with relapsed/refractory multiple myeloma (RRMM). At a median of 16.9 months in the primary analysis, KdD demonstrated superior efficacy and a deeper response compared with Kd. These benefits were maintained after an additional 11 months.

Landgren and colleagues report findings from a subgroup analysis that evaluated outcomes based on cytogenetic risk. In this analysis, 466 patients with RRMM were randomly assigned 2:1, KdD to Kd (312 patients were in the KdD group and 154 were in the Kd group). 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. Of these, 22.1% and 23.4% in the KdD and Kd groups had high-risk cytogenetics, respectively, with del(17p13) being the most common aberration. More than half of the patients were classified as standard-risk in each cohort, 57.1% in the KdD group and 64.3% in the Kd group.

Regardless of cytogenetic risk group, the overall response rate (ORR) was higher in the KdD group versus the Kd group: 81.2% versus 55.6% in high-risk patients and 86.5% versus 78.8% in standard-risk patients, respectively. Similar results were seen in patients with prior lenalidomide exposure: a higher ORR was observed with KdD compared with Kd in these patients across cytogenetic risk groups. ORR in high-risk patients was 84.6% in the KdD group versus 66.7% in the Kd group, and it was 79.2% versus 73.1% among 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 it was 85.8% with KdD and 76.7% with Kd in standard-risk patients. For all risk groups, progression-free survival (PFS) favored KdD over Kd. The median PFS for patients with high-risk cytogenetics with KdD was 11.2 months versus 7.4 months with Kd, whereas the median PFS in standard-risk patients was not reached with KdD and was 16.6 months with Kd.

The data from this subgroup analysis support the results from the CANDOR study and show improved responses with the addition of daratumumab to Kd. Although this study may be limited by small patient numbers in some subgroups and by the 84 patients with unknown cytogenetic risk, these findings support the use of KdD in RRMM patients regardless of cytogenetic risk.

Source

Landgren O, Weisel K, Rosinol L, et al. Subgroup analysis based on cytogenetic risk in patients with relapsed or refractory multiple myeloma in the CANDOR study. Br J Haematol. May 24, 2022. Epub ahead of print.

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