Management of multiple myeloma (MM) can be challenging because patients often relapse or become refractory to treatment. Isatuximab (Isa) is an anti-CD38 monoclonal antibody that demonstrated significant improvement in progression-free survival (PFS) in combination with pomalidomide and dexamethasone (Pd) compared with Pd alone in the phase 3 trial, ICARIA-MM. Currently, Isa is approved in combination with Pd for patients with relapsed/refractory MM (RRMM) after ≥2 previous lines of therapy. Before its approval, Isa-Pd was available under an early access program (EAP) in France for patients with RRMM who have received ≥2 previous lines of therapy. At the 2022 International Myeloma Society annual meeting, Leleu and colleagues reported results from an interim analysis of the IMAGE study, a noninterventional, retrospective cohort study of patients with RRMM who received ≥1 previous doses of Isa under the EAP from July 2019 to September 2020.
A total of 294 patients with RRMM were included in the effectiveness population, and 299 patients with RRMM were included in the safety population. Effectiveness end points included PFS, overall survival (OS), overall response rate (ORR), very good partial response (VGPR), partial response (PR), time to best response, time to next therapy (TTNT), and PFS under next therapy. The effectiveness analysis was conducted in patients with ≥1 year of follow-up after initiation of Isa. In contrast to ICARIA-MM, the IMAGE study included patients with only 1 previous line of therapy and patients who were refractory to daratumumab. In all, 24.8% of patients permanently discontinued Isa due to toxicity (6.8%), disease progression (63.0%), or other reasons (30.1%).
After a median follow-up of 14.2 months, the median PFS was 12.4 months (95% confidence interval [CI], 9.0-15.0), which is comparable to the median PFS of 11.1 months (95% CI, 7.8-13.8) in the Isa-Pd arm of the ICARIA-MM study. In patients with 1 previous line of therapy, the median PFS was not reached (NR; 95% CI, 9.6-NR); in patients with 2 previous lines of therapy, median PFS was 13.6 months (95% CI, 10.2-NR); and in patients with ≥3 previous lines of therapy, median PFS was 7.6 months (95% CI, 4.4-11.8). Median TTNT was also comparable to the ICARIA-MM study: TTNT was 15.2 months in the IMAGE study and 15.5 months in ICARIA-MM. However, ORR (46.3%) was lower in the IMAGE study compared with ICARIA-MM (63%). VGPR and PR were comparable between the IMAGE study and a real-world study of Isa plus Pd in patients with RRMM conducted in the United Kingdom: VGPR was 27.9% in the IMAGE study versus 31.8% in the UK study, and PR was 41.5% versus 34.6% in the UK study.1 Median OS was not reached in the IMAGE study (95% CI, 18.9-NR), whereas it was 24.6 months (95% CI, 20.3-31.3) in ICARIA-MM. A total of 26.4% of patients reported ≥1 adverse event (AE) in the IMAGE study. Of all grades, the most common AEs (occurring in ≥5% of patients) were neutropenia (9.4%) and thrombocytopenia (5%). Finally, 1.3% and 3% of patients discontinued Isa and Isa-Pd, respectively, due to ≥1 AE. Secondary primary malignancy was reported in 1 patient.
Overall, the IMAGE study, despite some population differences, demonstrated similar median PFS outcomes compared with ICARIA-MM. This study showed the effectiveness of Isa plus Pd in real-life context in a French population and supports its use as standard-of-care treatment in patients with RRMM.
- Djebbari F, Rampotas A, Vallance G, et al. Efficacy of isatuximab with pomalidomide and dexamethasone in relapsed myeloma: results of a UK-wide real-world dataset. Hemasphere. 2022;6(6):e738.
Source: Leleu X, Lafore R, Iaquinta D, et al. Isatuximab plus pomalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma (RRMM) in real-life context: interim analysis of the retrospective IMAGE study. Poster presented at: International Myeloma Society Annual Meeting; August 25-27, 2022; Los Angeles, CA.