Isatuximab Plus KRd Treatment Improved Rate of MRD Negativity in Patients With Newly Diagnosed MM
The study results also demonstrated isatuximab had safety and tolerability profiles that were consistent with other clinical trials.
Results from a phase 3 trial evaluating isatuximab (Sarclisa; Sanofi) in combination with carfilzomib, lenalidomide, and dexamethasone (KRD) demonstrated a statistically significant improvement in the rate of minimal residual disease (MRD) negativity after autologous stem cell transplant (ASCT) consolidation in patients with newly diagnosed multiple myeloma (MM) who were eligible for transplant. In addition, the safety and tolerability of isatuximab observed in the trial were consistent with the safety profiles in other clinical trials.
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Isatuximab, which is a monoclonal antibody that binds to an epitope on the CD38 receptor on MM cells, induces antitumor activity by working through multiple mechanisms of action and immunomodulatory activities, such as apoptosis. CD38 is a potential target for antibody-based therapeutics due to it being highly and uniformly expressed on the surface of MM cells.
The randomized, open-label phase 3 IsKia trial enrolled a total of 302 patients with newly diagnosed MM who were eligible for transplant. Patients were randomly assigned into 1 of 2 arms, with 1 group receiving an intravenous infusion of isatuximab once weekly for the first 4 weeks of cycle 1, then every other week for the rest of the induction and consolidation periods, then every 4 weeks during the light consolidation period. Both patient arms received induction with four 28-day cycles of KRd followed by cyclophosphamide and stem cell collections, 200 mg/m2 of chemotherapy with melphalan followed by ASCT, 4 28-day cycles of KRd light consolidation, and 12 cycles of KRd light consolidation.
The primary endpoint of the study was the rate of MRD negativity by next-generation sequencing after consolidation in the intent-to-treat population, and key secondary endpoints were the rate of next-generation sequencing MRD negativity after induction and progression-free survival. MRD rates were evaluated in an ITT analysis.
In the ITT analysis, the primary endpoint of rate of MRD negativity using next generation sequencing after consolidation for patients who received isatuximab combination therapy (n = 151) was approximately 77%, compared to those who received KRd alone (n = 151), which was 67% (odds ratio [OR] 1.67; p = 0.049). In addition, the rates of MRD negativity were 67% and 48%, respectively. The MRD negativity benefit was retained in all subgroups analyzed with similar benefit in both standard-risk and high-risk patients. Further, a statistically significant difference in MRD negativity rates after induction with isatuximab in combination with KRd compared to KRd alone (10-5: 45% vs 26%, p < 0.001; 10-6: 27% vs 14%, p = 0.004).
Rates of hematologic adverse events (AEs) grade 3 or higher were 40% vs 30%, and rates of non-hematologic AEs were 41% versus 37% for the isatuximab combination treatment versus KRd alone, respectively. Overall, discontinuation rates due to AEs were similar in both treatment arms (7% and 5%, respectively), with a total of 4 treatment-related deaths recorded across both arms (isatuximab arm: n = 3; KRd arm: n = 1).
“The statistically significant rates of MRD negativity observed with [isatuximab] combination therapy further support our belief in [isatuximab] as a potential best-in-class therapy. Effective front-line treatment is critical for newly diagnosed patients, because achieving undetectable levels of disease early in the treatment journey may lead to better long-term outcomes,” said Peter Adamson, MD, global development head, oncology, Sanofi, in a press release. “We look forward to our continued collaboration with the EMN to explore the potential of this novel combination regimen for those with transplant-eligible, newly diagnosed MM.”
Reference
Sanofi. Press Release: Sarclisa® (isatuximab) plus KRd significantly improved rate of minimal residual disease negativity in transplant-eligible patients with newly diagnosed multiple myeloma versus KRd alone. News release. December 10, 2023. Accessed January 9, 2024. https://finance.yahoo.com/news/press-release-sarclisa-isatuximab-plus-003100986.html
