Medically reviewed by Dr. Samuel Sarmiento, M.D., MPH on August 3, 2023
The combination of isatuximab, carfilzomib, and dexamethasone was found to be safe and efficacious for the treatment of relapsed multiple myeloma.
Triplet regimens consisting of a proteasome inhibitor or immunomodulatory drug, a monoclonal antibody, and dexamethasone have substantially improved clinical outcomes in relapsed and refractory multiple myeloma (MM) patients.
A study in the Blood Cancer Journal evaluated the longer-term outcomes of a regimen comprising anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) in relapsed MM patients. It demonstrated high efficacy and a manageable safety profile.
Study Design and Population
A follow-up analysis of the Phase 3 trial IKEMA was conducted to evaluate longer-term outcomes. At the data cut-off, the median follow-up was 44 months; 49 (27.4%) patients in the Isa-Kd arm and 11 (8.9%) in the Kd arm were still on the treatment. Baseline demographic and disease characteristics were comparable between the arms. The median age was 65 in the Isa-Kd arm and 63 in the Kd arm.
Isa-Kd Showed Significant Progression-Free Survival Benefits Across Patient Subgroups
There was a 42% reduction in the risk of progression or death with Isa-Kd vs. Kd. The median progression-free survival reached with Isa-Kd was 35.7 months vs. 19.2 months with Kd. Subgroup analyses by patient characteristics and prognostic factors showed consistent benefits with Isa-Kd vs. Kd across all subgroups.
Comparison of Responses in the Intent-To-Treat Population
The overall response rates were comparable between the Isa-Kd and Kd arms (86.6% and 83.7%, respectively); however, deeper responses were observed with Isa-Kd vs. Kd in the intent-to-treat population, with the stringent-complete response/complete response rate being 44.1% with Isa-Kd and 28.5% with Kd, and 8 additional complete responses in Isa-Kd and 1 additional complete response in Kd compared with the interim analysis.
Improved MRD negativity rate was seen in the Isa-Kd arm (33.5%) compared to the Kd arm (15.4%). The MRD negativity and complete response rate was 26.3% with Isa-Kd vs. 12.2% with Kd.
Time-to-Next-Treatment and Anti-Myeloma Therapy in Isa-Kd vs. Kd Treatment
Isa-Kd also demonstrated more delayed time-to-next-treatment than Kd (44.9 vs. 25 months, respectively). Further anti-myeloma therapy was taken up by fewer patients on Isa-Kd vs. Kd (44.1% vs. 64.2%, respectively).
Safety Profile of Isa-Kd Compared to Kd in Long-Term Follow-up
Adding Isa to Kd did not increase the incidence of treatment-emergent adverse events (TEAEs) with fatal outcomes or TEAEs leading to treatment discontinuation. A 10% difference in all-causality serious TEAE incidence between Isa-Kd and Kd was noted and was related to the longer treatment with Isa-Kd. Grade ≥3 TEAEs were more frequent in Isa-Kd vs. Kd, with an event rate per patient-year of 1.08 with Isa-Kd vs. 0.97 with Kd.
With an additional 2-year follow-up, the incidence of treatment-emergent fatal events remained similar between the arms, and the event rate per patient-year remained identical to that at the interim analysis. The most common TEAEs were infusion reactions, diarrhea, hypertension, upper respiratory tract infection, fatigue, anemia, neutropenia, and thrombocytopenia.
Source:
Martin, T. G., Dimopoulos, M. A., Mikhael, J., Yong, K., Capra, M., Facon, T., Hájek, R., Špička, I., Baker, R., Kim, K., Martinez, G., Min, C., Pour, L., Leleu, X., Oriol, A., Koh, Y., Suzuki, K., Casca, F., Macé, S., . . . Moreau, P. (2023). Isatuximab, carfilzomib, and dexamethasone in patients with relapsed multiple myeloma: updated results from IKEMA, a randomized Phase 3 study. Blood Cancer Journal, 13(1). https://doi.org/10.1038/s41408-023-00797-8
