Isatuximab Plus Pomalidomide and Dexamethasone: New Standard of Care for Relapsed/Refractory MM

Isatuximab plus pomalidomide and dexamethasone resulted in improved overall survival (OS) for patients with refractory or relapsed (R/R) multiple myeloma (MM) compared with pomalidomide and dexamethasone alone, and is a new standard of care for such patients, according to follow-up analysis from the phase 3 ICARIA-MM trial.

In the multicenter, open-label study, a total of 307 adult patients were randomized. Subjects had to have received at least 2 previous lines of therapy, including lenalidomide and a proteasome inhibitor, and had an Eastern Cooperative Oncology Group performance status of 0–2.

In the treatment arm, intravenous isatuximab 10 mg/kg was administered on days 1, 8, 15, and 22 of the first 4-week cycle, and then on days 1 and 15 of subsequent cycles. Both groups received oral pomalidomide 4 mg on days 1–21 of each cycle, and weekly oral or intravenous dexamethasone 40 mg (20 mg if aged ≥75 years) on days 1, 8, 15, and 22 of each cycle.

For purposes of the analysis, they were stratified by number of previous treatment lines (2–3 vs >3) to isatuximab–pomalidomide–dexamethasone (isatuximab group) or pomalidomide–dexamethasone (control group), and followed until disease progression, unacceptable toxicity, or withdrawal of consent.

The researchers conducted an updated overall survival (OS) analysis at 24 months after primary analysis. Participation in the treatment arm resulted in a 6.9-month difference in median OS: 24.6 months (95% CI 20.3–31.3) in the isatuximab group and 17.7 months (14.4–26.2) in the control group (HR 0.76 [95% CI 0.57–1.01], P = .028) respectively.

Serious treatment-emergent adverse events were observed in 111 (73%) patients in the isatuximab group and 90 (60%) patients in the control group. Median follow-up at data cutoff (Oct 1, 2020) was 35.3 months.  Final overall survival follow-up analysis is ongoing.

Source:
Richardson P, Perrot A, San-Miguel J, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022 Mar;23(3):416-427. doi:10.1016/S1470-2045(22)00019-5.