FDA approves isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma
Regulatory approval: On September 20, 2024, the FDA approved isatuximab-irfc (Sarclisa) in combination with bortezomib, lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant. Approval was supported by the phase 3 IMROZ trial, which showed improved independent review committee–assessed PFS versus VRd alone (HR 0.60; p=0.0009); median PFS was not reached with Isa-VRd and was 54.3 months with VRd.
FDA approval (2024-09-20): isatuximab-irfc + VRd for transplant-ineligible NDMM
The US Food and Drug Administration (FDA) approved isatuximab-irfc (Sarclisa; Sanofi-Aventis U.S. LLC) in combination with bortezomib, lenalidomide, and dexamethasone (Isa-VRd) for adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT).
Key evidence
Efficacy and safety were evaluated in IMROZ (NCT03319667), an open-label, randomized, active-controlled phase 3 trial in patients with newly diagnosed multiple myeloma not eligible for ASCT; enrollment was limited to patients ≤80 years. A total of 446 patients were randomized 3:2 to Isa-VRd vs VRd.
The primary endpoint was progression-free survival (PFS) assessed by an independent review committee using International Myeloma Working Group criteria. IMROZ reported a 40% reduction in the risk of progression or death with Isa-VRd (HR 0.60; 95% CI 0.44–0.81; p=0.0009). Median PFS was not reached in the Isa-VRd arm (95% CI: NR–NR) and was 54.3 months with VRd (95% CI: 45.2–NR).
Safety and dosing
Most common adverse reactions (≥20%) included URTI, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 infection. Recommended isatuximab-irfc dose: 10 mg/kg IV (actual body weight).
The application received priority review and orphan drug designation.