- Addition of the anti CD38 antibody isatuximab to pomalidomide and low-dose dexamethasone significantly improved progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM).
Why this matters
- Therapies to improve survival in RRMM patients are an unmet medical need.
- Isatuximab/pomalidomide/low-dose dexamethasone (IsaPd) is a new treatment option for the management of RRMM.
- The phase 3 ICARIA-MM trial enrolled 307 patients with RRMM who received ≥2 prior lines (including lenalidomide and a proteasome inhibitor) refractory to last therapy.
- Patients were randomly assigned (1:1) to receive IsaPd or pomalidomide/low-dose dexamethasone (Pd) until disease progression or unacceptable toxicity.
- The primary endpoint was PFS; the secondary endpoints were overall response rate (ORR) and overall survival (OS).
- Fewer discontinuations were registered in the IsaPd arm vs the Pd arm (87/154 vs 114/153).
- At median follow-up of 11.6 months, median PFS was 11.5 months in the IsaPd arm and 6.5 months in the Pd arm (HR 0.596; P=0.001).
- PFS benefit obtained with IsaPd was consistent across all major subgroups.
- Addition of isatuximab to Pd resulted in a significant improvement in ORR (60.4% vs 35.3%, P
- With median not reached in either arm, a trend to OS improvement was observed in the IsaPd arm (HR 0.687), however OS data are immature.
- Despite more grade ≥3 treatment emergent adverse events (86.8% vs 70.5%), addition of isatuximab to Pd did not increase mortality (7.9% vs 9.4%) or events leading to discontinuation (7.2% vs 12.8%).
- Anaemia and thrombocytopenia were similar in both arms, grade 4 neutropenia was more frequent in the IsaPd arm.
“Progression free survival with IsaPd is the longest observed to date in this patient population. Importantly, the safety profile was generally manageable with appropriate supportive care and maintained patient quality of life.” Paul G. Richardson, Dana-Farber Cancer Institute, Harvard Medical School, Boston (MA, USA), primary investigator of the ICARIA-MM trial.