Phase III ICARIA-MM trial of SAR 650984 shows reduced risk in multiple myeloma.

Pivotal Phase III ICARIA-MM trial results demonstrated that SAR 650984 (isatuximab), from Sanofi, added to pomalidomide and dexamethasone (isatuximab combination therapy) showed statistically significant improvements compared to pomalidomide and dexamethasone (pom-dex) alone in patients with relapsed/refractory multiple myeloma (RRMM). Isatuximab combination therapy showed a statistically significant improvement in progression free survival (HR 0.596, 95% CI 0.44-0.81, p=0.001), and the median progression free survival was longer in the isatuximab combination therapy arm (11.53 months, 95% CI: 8.936 to 13.897) than pom-dex alone (6.47 months, 95% CI: 4.468 to 8.279). Also of note, isatuximab combination therapy demonstrated a significantly greater overall response rate, compared to pom-dex alone (60% vs. 35%, p<0.0001).

In additional analyses, isatuximab combination therapy compared to pom-dex alone showed a treatment benefit consistent across multiple subgroups, including patients 75 years and older, patients with renal insufficiency, and patients who were refractory to lenalidomide. The results presented above were based on an independent review committee assessment. In addition, the following results favored isatuximab combination therapy: Isatuximab combination therapy demonstrated significantly higher very good partial response (VGPR) rate compared to pom-dex (31.8% vs. 8.5%, respectively, p<0.0001) and a longer duration of response compared to pom-dex alone (median 13.27 months vs. 11.07 months, respectively). Among patients who achieved a response, isatuximab combination therapy demonstrated faster median time to first response compared to pom-dex alone (35 days vs. 58 days, respectively).

Time to next treatment was longer with isatuximab combination therapy compared to pom-dex alone (median not reached vs. 9.1 months, HR=0.538). Data at the time of analysis showed a trend towards an overall survival benefit associated with isatuximab combination therapy. Final data on overall survival will be reported when available. Adverse events (AEs) of Grade >=3 were observed in 86.8% of isatuximab combination therapy patients vs. 70.5% of pom-dex patients. These findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.