Real-World Experience with Isatuximab in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM): Iona-MM Second Interim Analysis

Abstract

Introduction: Isatuximab (Isa) is an anti-CD38 monoclonal antibody that targets a specific CD38 epitope and induces myeloma cell death via multiple mechanisms. Based on the Phase 3 ICARIA-MM and IKEMA studies, Isa plus pomalidomide (P) and dexamethasone (d; Isa- Pd) or carfilzomib (K) and d (Isa-Kd), respectively, are approved in patients (pts) with RRMM. Currently, limited real-world evidence (RWE) exists for pts treated with Isa-Pd/Isa-Kd. This first interim analysis of the non-interventional, observational IONA-MM study (NCT04458831) details baseline characteristics, treatment exposure, and TEAEs for pts with RRMM treated with Isa in the real-world setting. Methods: Pts ≥18 years old with RRMM who received ≥1 prior treatment line were eligible for the study. Pts were enrolled prospectively and retrospectively (Isa-exposed ≤3 months pre-enrollment). The treating physician determined Isa treatment prior to and independent of enrollment; treatment duration was based on local prescribing regulations. AEs and laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Between 13 August 2020 and 22 February 2022, 112 pts were enrolled across 38 study sites spanning 6 countries and received ≥1 dose of Isa-Pd (n=81), Isa-Kd (n=26), or other Isa regimens (n=5). Compared to the baseline characteristics in the corresponding Phase 3 Isa studies, a higher proportion of pts who received Isa-Pd/Isa-Kd in IONA-MM were ≥75 years-old and were ISS stage III, and a lower proportion of Isa-Kd pts had high-risk cytogenetics. Among the pts in the Isa-Pd and Isa-Kd groups, 31.5% and 23.1% respectively, had received ≥4 prior lines of therapy. Among the pts in IONA-MM study, 90.1% of pts in Isa-Pd and all pts (100%) in Isa-Kd groups received prior medications for MM. At data cutoff, median (min-max) duration of Isa exposure was 5.4 (0-18.8) months for Isa-Pd and 6.2 (0-10.6) months for Isa-Kd, with 79.0% pts still receiving Isa-Pd and 74.1% still receiving Isa-Kd. All-grade TEAEs occurred in 52 (64.2%) pts with Isa- Pd and 16 (61.5%) pts with Isa-Kd; Grade 3-4 TEAEs in 36 (44.4%) and 10 (38.5%) pts; serious TEAEs in 21 (25.9%) and 8 (30.8%) pts; fatal TEAEs during study treatment in 4 (4.9%; 2 [sepsis], 1 [septic shock], and 1 [failure to thrive]) pts and 1 (3.8%; pneumonia) pt; and TEAEs leading to Isa discontinuation in 6 (7.4%) and 3 (11.5%) pts with Isa-Pd and Isa-Kd, respectively. The most common all-grade TEAE was neutropenia in the Isa-Pd arm, and diarrhea in the Isa-Kd arm. Response data are forthcoming. Discussion: In this IONA-MM first interim analysis, we report comparable pt baseline characteristics to those seen in ICARIA-MM/IKEMA with a few imbalances. Both Isa-Pd and Isa-Kd have a manageable safety profile in routine clinical practice. These data provide RWE to support the use of Isa in RRMM outside of clinical trials and in wider populations. Enrollment in IONA-MM is ongoing and will continue until the sample size (1100 pts) is reached.