Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients

Abstract

Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings.

Keywords: isatuximab; multiple myeloma; proteasome inhibitors; real life.

FIGURE 1

Progression‐free survival (PFS) in the entire Isa‐Kd‐treated cohort stratified by features. (A) PFS of patients with high (red) versus standard genetic risk (blue). (B) PFS of patients with extramedullary disease (EMD) (red) versus without EMD (blue). (C) PFS of patients treated after 1 (red) versus 2–3 prior lines of therapy (blue). (D) PFS of patients with R‐ISS stages II and III (red) versus I (blue). (E) PFS of patients daratumumab‐ (red) versus not daratumumab‐exposed (blue). (F) PFS of patients who received a ≤ 12 (red) versus > 12 months (blue) lenalidomide maintenance. (G) PFS of patients who received a ≤ 24 (red) versus > 24 months (blue) lenalidomide maintenance. (H) PFS of patients who achieved a ≥ VGPR (red) versus < VGPR (blue). A p < 0.05 was considered statistically significant. HR, hazard ratio.

FIGURE 2

Progression‐free survival (PFS) in the cohort treated with Isa‐Kd as second‐line therapy stratified by features. (A) PFS of patients with high (red) versus standard genetic risk (blue). (B) PFS of patients who were daratumumab‐ (red) versus not daratumumab‐exposed (blue). (C) PFS of patients who received a ≤ 12 (red) versus > 12 months (blue) lenalidomide maintenance. (D) PFS of patients who received a ≤ 24 (red) versus > 24 months (blue) lenalidomide maintenance. (E) PFS of patients who achieved a ≥ VGPR (red) versus < VGPR (blue). (F) PFS of patients with R‐ISS stages II and III (red) versus I (blue). A p < 0.05 was considered statistically significant. HR, hazard ratio.