ICARIA-MM was a phase 3 trial that demonstrated significant improvement in progression-free survival (PFS) with isatuximab (Isa) in combination with pomalidomide and dexamethasone (Pd) versus Pd alone in patients with relapsed/refractory multiple myeloma (RRMM). Similarly, the IKEMA study was a phase 3 trial showing that Isa plus carfilzomib and dexamethasone (Kd) significantly improved PFS in patients with RRMM versus Kd alone. Based on these studies, Isa is currently approved in combination with Pd for patients with RRMM who have received ≥2 prior lines of therapy and in combination with Kd in patients with RRMM who have received 1 to 3 prior lines of therapy. Although these clinical trials demonstrated superiority with the addition of Isa, real-world evidence with Isa-Pd and Isa-Kd treatment in patients with RRMM is limited. At the 2022 International Myeloma Society Meeting, Martin and colleagues presented interim results from the IONA-MM registry study, an ongoing, noninterventional, multinational, observational study of patients with RRMM treated with Isa in the real-world setting.
Patients with RRMM were enrolled prospectively and retrospectively (Isa exposure ≤3 months pre-enrollment) into the study and had received ≥1 prior lines of therapy. Independent of enrollment, the treating physician determined Isa treatment. Baseline assessments were conducted up to 4 weeks prior to Isa initiation. Beginning at Isa initiation, the treatment observation period included routine clinical assessments obtained at 4 weeks after initiation and every 3 months thereafter up to 30 days after discontinuation. Follow-up assessments were then collected for each patient for a maximum of 6 months 30 days after Isa discontinuation and continued until loss of follow-up, withdrawal of consent, death, or study end.
A total of 112 patients were included in the first interim analysis; participants received ≥1 dose of Isa-Pd (81 patients), Isa-Kd (26 patients), or another Isa regimen (5 patients). Compared with baseline characteristics of patients in IKEMA and ICARIA-MM, this study included more patients aged ≥75 years and with International Staging System stage III disease. In addition, the study included a lower proportion of high-risk cytogenetics in patients receiving Isa-Kd. At data cutoff, 79.0% of patients were still receiving Isa-Pd and 74.1% of patients were still receiving Isa-Kd. The median duration of exposure was 5.4 months for Isa-Pd and 6.2 months for Isa-Kd. In the safety population, incidences of all-grade, grade 3 to 4, and serious treatment-emergent adverse events (TEAEs) with Isa-Pd and Isa-Kd treatments were lower than that seen in IKEMA and ICARIA-MM. TEAEs leading to discontinuation of Isa were reported in 7.4% of patients receiving Isa-Pd and 11.5% of patients receiving Isa-Kd. Grade 5 TEAEs occurred in 4.9% of patients in the Isa-Pd group and 3.8% of patients in the Isa-Kd group. Of all grades, the most common TEAE (≥5%) was neutropenia in the Isa-Pd group (22.2%) and diarrhea in the Isa-Kd group (15.4%).
Although this study is ongoing, the first interim analysis provides real-world evidence of treatment with Isa in patients with RRMM, showing mostly comparable baseline characteristics to phase 3 trials and a tolerable safety profile. The study is continuing to recruit patients and enrollment will continue until a sample size of 1100 patients is reached.
Source
Martin T, Becsac M, Cavo M, et al. Real-world experience with isatuximab with relapsed and/or refractory multiple myeloma (RRMM): IONA-MM first interim analysis. Poster presented at: International Myeloma Foundation; August 25-27, 2022; Los Angeles, CA. Poster P-258.