Updated PFS and Depth of Response from IKEMA Show Improvement in PFS with Isa-Kd

The primary interim analysis of the IKEMA study showed that the anti-CD38 antibody isatuximab (Isa) in combination with carfilzomib and dexamethasone (Kd) demonstrated significant improvement in progression-free survival (PFS) with manageable toxicities and good tolerability.1 Subsequently, Isa in combination with Kd has received numerous global approvals for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) after ≥1 prior lines of therapy.

At the 2022 European Society for Medical Oncology hybrid plenary meeting, Moreau and colleagues presented updated PFS and depth-of-response data from the IKEMA trial. Prespecified analysis explored longer term results; the primary end point was PFS, and secondary end points included overall response rate, minimal residual disease (MRD)-negativity rate, complete response rate, overall survival (OS), and safety at 159 PFS events.2 A total of 179 patients were randomly assigned to receive Isa-Kd, and 123 patients were assigned to the Kd-only group. Patient demographics and baseline characteristics were similar between the 2 groups.

After a median follow-up of 44 months, 49 (27.4%) patients were still receiving treatment with Isa-Kd, whereas 11 (8.9%) patients were still receiving Kd treatment alone. In the updated analysis, the median PFS with Kd alone was 19.2 months versus 35.7 months with Isa-Kd.2 This PFS of 35.7 months is the longest PFS when using a proteasome inhibitor backbone in the RRMM setting. The PFS benefit was consistent across subgroups, regardless of age, prior lines of therapy, or prior proteasome inhibitor or immunomodulatory drug treatment. Furthermore, with the addition of Isa to Kd, the probability of relapse or death was reduced by 42%. The MRD-negativity rate in the intention-to-treat (ITT) population was 33.5% with Isa-Kd versus 15.4% with Kd alone. In patients reaching complete response, the MRD-negativity rate was 26.3% with Isa-Kd versus 12.2% with Kd alone. In the ITT population, time to next treatment was delayed with Isa-Kd use: 44.9 months versus 25.0 months with Kd alone. The OS was not mature at the time of this analysis; however, a final OS is planned for 3 years after the interim PFS analysis. Safety findings were consistent with the interim analysis, and the addition of Isa did not increase fatal treatment-related adverse events. The most common adverse events were infusion reactions, although most were grade 1 or 2.2

These results, after a follow-up of 44 months, are consistent with findings from the interim analysis and demonstrate improvement in PFS with Isa-Kd, with a median PFS of almost 3 years.2 Researchers concluded that these findings support the use of Isa-Kd as standard of care for patients with RRMM.

Sources

  1. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021;397(10292):2361-2371.
  2. Moreau P, Dimopoulos MA, Mikhael J, et al. Updated progression-free survival (PFS) and depth of response in IKEMA, a randomized phase III trial of isatuximab, carfilzomib and dexamethasone (Isa-Kd) vs Kd in relapsed multiple myeloma (MM). Presented at: European Society for Medical Oncology hybrid plenary meeting; May 19-20, 2022; Berlin, Germany.

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