On 20 September 2024, the US Food and Drug Administration (FDA) approved isatuximab-irfc (Sarclisa, Sanofi-Aventis U.S. LLC) with bortezomib, lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT).
Efficacy was evaluated in IMROZ (NCT03319667), an open-label, randomised, active-controlled phase III study in patients with newly diagnosed multiple myeloma who were not eligible for ASCT. Enrolment was limited to patients 80 years of age and younger. A total of 446 patients were randomised (3:2) to receive either isatuximab-irfc with bortezomib, lenalidomide, and dexamethasone (Isa-VRd) or bortezomib, lenalidomide, and dexamethasone (VRd).
The main efficacy outcome measure was progression-free survival (PFS) as assessed by an independent review committee based on International Myeloma Working Group criteria. IMROZ demonstrated an improvement in PFS in the Isa-VRd arm with a 40% reduction in risk of disease progression or death (hazard ratio 0.60, 95% confidence interval [CI] 0.44, 0.81; p-value = 0.0009); the median PFS was not reached (NR, 95% CI NR, NR) in the Isa-VRd arm and was 54.3 months (95% CI 45.2, NR) in the VRd arm.
The most common adverse reactions (≥20%) were upper respiratory tract infection, diarrhoea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral oedema, rash, infusion-related reaction, insomnia, and COVID-19 infection.
The recommended isatuximab-irfc dose is 10 mg/kg actual body weight administered as an intravenous infusion.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and orphan drug designation.
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