Real-World Comparison of Carfilzomib, Lenalidomide, and Dexamethasone Versus Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma: KMM2004 Study

Abstract

Background: Lenalidomide-based triplet regimens, specifically carfilzomib, lenalidomide, and dexamethasone (KRd) and ixazomib, lenalidomide, and dexamethasone (IRd), are recognized as effective treatments for relapsed/refractory multiple myeloma (RRMM). Since 2020, South Korea's National Health Insurance Service has covered these combinations, prompting a need for real-world comparisons of their efficacy and safety. Methods: A retrospective analysis of 182 RRMM patients treated with KRd (112) or IRd (70) at 17 South Korean centers from May 2020 to April 2021 was conducted. Results: Better outcomes for the KRd were expected according to previous randomized controlled trials (RCT). However, there was no significant difference in the overall response rate between the two groups (89.1 vs. 87.0%, P =.67). Responses above very good partial response tended to be higher in the KRd (70.9 vs. 58.0%, P =.075), although not statistically significant. In terms of treatment maintenance, the two groups had a 9.3-month difference in progression-free survival, but it was not statistically significant (19.1 vs. 28.4 months, P =.08). Overall survival was longer for IRd (31.6 months vs. not achieved, P =.02). Analysis revealed that the proper toxicity control and dose modification have influenced these results. Subgroup analysis found no difference in treatment outcome between the two treatments in high-risk patients. Conclusions: Comparing the two treatments in the real-world revealed inconsistent outcomes from the predictions based on RCTs. The KRd showed an advantage in the depth of response, while the IRd showed an advantage in the duration of the response. The findings will be helpful in choosing the best strategies of treatment for patients with RRMM. © 2025