The incidence of multiple myeloma (MM) in Asian populations has been increasing, potentially due to rapid industrialization and longer lifespan. Isatuximab (Isa) added to carfilzomib (K) and dexamethasone (d) is approved in multiple countries for the treatment of patients with relapsed/refractory MM (RRMM).
In the phase 3 IKEMA trial, Isa-Kd significantly improved progression-free survival (PFS) and depth of response in patients with RRMM versus Kd alone. Kim and colleagues reported findings from a post-hoc subgroup analysis from this trial of Isa-Kd versus Kd to evaluate the safety and efficacy of Isa-Kd in East Asian patients.
Patients had received 1 to 3 prior lines of therapy and were then stratified by number of prior lines. The primary end point was PFS, and secondary end points included overall response rate (ORR), very good partial response or better (≥VGPR), minimal residual disease (MRD) negativity, and complete response (CR) rate.
In this subgroup analysis, efficacy was assessed in the intention-to-treat (ITT) population. A total of 46 East Asian patients with RRMM were enrolled, 19 Japanese patients and 27 South Korean patients. Of these, 25 were randomly assigned to Isa-Kd and 21 to Kd alone. Baseline characteristics were generally well-balanced and were similar to the IKEMA ITT population. Median PFS was not reached in either arm, although it was prolonged in the Isa-Kd arm compared with Kd alone. The ORR was 88% in the Isa-Kd arm, compared with 81% in the Kd arm. More patients in the Isa-Kd arm, 80%, achieved ≥VGPR, compared with 52% in the Kd arm. In addition, MRD negativity (44% vs 10%), CR (44% vs 24%), and CR with MRD negativity (36% vs 5%) were improved with Isa-Kd versus Kd alone, respectively. Median time to first and best responses with Isa-Kd were 1.02 months and 2.96 months, whereas time to first and best responses with Kd alone were 1.17 months and 5.65 months. No clinically meaningful change in quality of life was observed in Isa-Kd patients throughout the treatment period.
The subgroup safety population included 44 East Asian patients. At cutoff, 16 patients in the Isa-Kd arm and 9 patients in the Kd arm were still receiving treatment. The median duration of treatment exposure was 82 weeks in the Isa-Kd arm versus 63 weeks in the Kd arm. The incidence of grade ≥3 treatment-related adverse events was higher in the Isa-Kd group compared with Kd alone, 79% versus 55%, respectively. The rate of serious treatment-related adverse events was similar in both arms, 46% versus 50%, whereas the rate of discontinuation due to adverse events was lower in the Isa-Kd arm, 4%, versus the Kd-alone arm, 10%.
These findings are consistent with the overall IKEMA population and demonstrated improved efficacy and safety with Isa-Kd versus Kd alone in East Asian patients with RRMM.
Source
Kim K, Min C-K, Koh Y, et al. Isatuximab plus carfilzomib and dexamethasone in East Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis. Int J Hematol. May 17, 2022. doi: 10.1007/s12185-022-03378-w. Online ahead of print.