On September 20, the U.S. Food and Drug Administration (FDA) approved the monoclonal antibody 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 (ASCT).
Efficacy and Safety
Efficacy was evaluated in the open-label, randomized, active-controlled phase III IMROZ trial (ClinicalTrials.gov identifier NCT03319667) in patients with newly diagnosed multiple myeloma who were not eligible for ASCT. Enrollment was limited to patients aged 80 and younger. A total of 446 patients were randomly assigned (3:2) to receive either isatuximab with bortezomib, lenalidomide, and dexamethasone (VRd) or VRd alone.
The main efficacy outcome measure was progression-free survival as assessed by an independent review committee based on International Myeloma Working Group criteria. An improvement in progression-free survival was reported with isatuximab plus VRd, with a 40% reduction in the risk of disease progression or death (hazard ratio = 0.60 [95% confidence interval (CI) = 0.44–0.81]; P = .0009); the median progression-free survival was not reached (NR; 95% CI = not reached to not reached) in the isatuximab-plus-VRd arm and was 54.3 months (95% CI = 45.2 months to not reached) in the VRd arm.
The most common adverse reactions (≥ 20%) were upper respiratory tract infection, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataracts, constipation, peripheral edema, 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. For the dosage recommendations for the other drugs, see the prescribing information.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
