Isatuximab-irfc Plus Bortezomib, Lenalidomide, And Dexamethasone Approved For Newly Diagnosed Multiple Myeloma
Expert Perspectives · Lyn Brook · 2024-09-25
The FDA has granted approval to isatuximab-irfc (Sarclisa®, Sanofi-Aventis U.S. LLC) plus bortezomib, lenalidomide, and dexamethasone for adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT).
Why it matters: “The approval of isatuximab as part of a quadruplet regimen for newly diagnosed non transplant-eligible multiple myeloma gives patients and clinicians a more aggressive option, provided patients are of appropriate performance status,” wrote Joseph Kalis, PharmD, BCOP, Ambulatory Oncology Clinical Pharmacy Specialist at the University of Colorado Health, regarding the IMROZ trial (NCT03319667), on which approval was based. “Daratumumab is currently approved in this space, but as part of a triplet regimen. Given the success of quadruplet regimens in transplant-eligible patients, the IMROZ data shouldn’t be a surprise to us. Rather, they grant further validity to the existing use of quadruplet regimens in patients not eligible for transplant”.
What they studied: Efficacy was measured in the phase 3, open-label, controlled trial which enrolled 446 patients ≤80 years of age with newly diagnosed multiple myeloma who were not eligible for ASCT. Patients were randomized 3:2 to receive either isatuximab-irfc plus bortezomib, lenalidomide, and dexamethasone (Isa-VRd) or VRd alone.
The primary efficacy outcome measured was progression-free survival as assessed by an independent review committee based on criteria from the International Myeloma Working Group.
What they found: An improved progression-free survival was demonstrated in the Isa-VRd arm with a 40% reduction in risk of disease progression or death. The median progression-free survival was not reached in the Isa-VRd arm and was 54.3 months in the VRd arm.
Adverse events: The most common adverse events experienced by ≥20% of those receiving isatuximab-irfc were upper respiratory tract infection, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 infection.
Conclusion: “I appreciate the inclusion of MRD negativity as a secondary endpoint in IMROZ, as it provides clinicians and patients with objective evidence that can be used to assess treatment options,” concluded Dr. Kalis. “The treatment landscape in multiple myeloma is as fluid as the cancer itself, with available agents mixed and matched based on each unique patient. It is tempting to state that isatuximab and daratumumab could be interchangeable based on existing data, but we have to rely on the patient populations, lines of therapy, and primary study endpoints to guide our decisions.”
Instructions: The recommended dosage of isatuximab-irfc is 10 mg/kg actual body weight administered as an intravenous infusion. Refer to the prescribing information for the dosing of the other drugs.