Isatuximab Plus Carfilzomib and Dexamethasone Demonstrates Efficacy, Safety as Standard-of-Care Treatment for Patients With R/R Multiple Myeloma

Longer-Term Follow-Up Analysis of the Phase 3 IKEMA Trial

A longer-term follow-up analysis of the phase 3 IKEMA trial published in Blood Cancer Journal indicated that the combination of anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) demonstrated efficacy and manageable safety as a standard-of-care treatment among patients with relapsed/refractory (R/R) multiple myeloma (MM). 

Thomas Martin, MD, University of California at San Francisco, San Francisco, California, and coauthors aimed to analyze previous results in a follow-up, prespecified analysis of the IKEMA study population and “evaluate longer term outcomes with [isatuximab plus carfilzomib-dexamethasone] vs [carfilzomib-dexamethasone] in patients with relapsed MM.” 

In the IKEMA study, 179 patients with R/R MM received isatuximab at 10 mg/kg intravenously during cycle 1 and subsequently every 2 weeks plus carfilzomib-dexamethasone, and 123 patients received carfilzomib-dexamethasone alone. All patients had previously undergone 1 to 3 lines of treatment. The primary endpoint was progression-free survival (PFS), and secondary endpoints included complete response, safety, and other efficacy and disease control results.

Consistent with the initial interim analysis, the addition of isatuximab to carfilzomib-dexamethasone demonstrated a significant prolongation of progression-free survival (hazard ratio [HR] 0.58, 95.4% confidence interval [CI], 0.42 to 0.79),  with a median PFS of 35.7 months (95% CI, 25.8 to 44.0) in the isatuximab plus carfilzomib-dexamethasone cohort compared to 19.2 months (95% CI, 15.8 to 25.0) in the carfilzomib-dexamethasone alone cohort. The PFS benefit was consistent across various subgroups, even among patients with poor prognosis. 

The stringent complete response rate was higher in the isatuximab plus carfilzomib-dexamethasone cohort (44.1%) compared to the carfilzomib-dexamethasone alone cohort (28.5%) (odds ratio: 2.09, 95% CI, 1.26 to 3.48). The analysis of minimal residual disease (MRD) negativity rate was 33.5% in the isatuximab plus carfilzomib-dexamethasone cohort and 15.4% in the carfilzomib-dexamethasone alone cohort (odds ratio: 2.78, 95% CI, 1.55 to 4.99). Similarly, the MRD negativity complete response rate was higher in the isatuximab plus carfilzomib-dexamethasone cohort (26.3%) compared to the carfilzomib-dexamethasone alone cohort (12.2%). Overall, the safety profile of this combination treatment was found to be consistent with prior interim analyses.

Dr Martin et al concluded, “the improvement in PFS observed in this updated analysis of IKEMA, with a [median] PFS of nearly 3 years, achievement of MRD negativity in a third of [isatuximab combined with carfilzomib and dexamethasone] treated patients, reaching MRD negativity and CR in >25% of them, and a manageable safety profile, further support [isatuximab combined with carfilzomib and dexamethasone] as a standard of care treatment for patients with relapsed MM.”

“The long-term benefit achieved in our study supports the use of the most effective, available drugs and combination therapies as early as possible in relapsed MM, in addition to the newly diagnosed MM setting, in order to gain the best outcomes,” they added.

Source: 

Martin T, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized phase 3 study. Blood Cancer J. 13, 72 (2023). doi:10.1038/s41408-023-00797-8