Subcutaneous isatuximab by on-body-injector plus bortezomib, lenalidomide, and dexamethasone in newly diagnosed transplant-ineligible multiple myeloma: ISASOCUT study

Abstract

Isatuximab–bortezomib–lenalidomide–dexamethasone (Isa-VRd) has emerged as a standard of care for newly diagnosed multiple myeloma transplant-ineligible patients. A subcutaneous (SC) formulation of isatuximab delivered via an on-body injector (OBI) has been developed to facilitate treatment administration. ISASOCUT is a prospective, multicenter, phase 2 study evaluating the efficacy and tolerability of Isa SC-VRd administered via OBI. SC isatuximab (1400 mg) was given weekly during cycle 1, then on days 1 and 15 through cycle 12 in combination with VRd, followed by monthly isatuximab–lenalidomide until progression. The primary endpoint was the rate of ≥very good partial response (VGPR) at 8 months. Seventy-four patients were treated, with a median age of 73 years. At 8 months, the primary endpoint was met, with a ≥VGPR rate of 88% (95% CI, 78–94, p < 0.001). Minimal residual disease negativity was achieved in 36% at 10⁻⁵ and 28% at 10⁻⁶. At a median follow-up of 21.2 months, 14-month progression-free and event-free survival rates were 93.1% and 91.7%, respectively. The median relative dose intensity of isatuximab was 91.8%, with 99.3% of injections successfully completed. Infusion-related reactions occurred in 5% of patients, mostly low grade. ISASOCUT met its primary endpoint and supports SC isatuximab via OBI as a feasible alternative to intravenous administration.