Dr Facon on the Rationale for Evaluating Isa-VRd in Transplant-Ineligible, Newly Diagnosed Multiple Myeloma

“The purpose was to assess the clinical benefit of adding isatuximab to VRd, considering that the patient population is elderly and still has an unmet medical need.”

Thierry Facon, MD, a professor of hematology in the Department of Hematology at Lille University Hospital, explained the rationale for evaluating isatuximab-irfc (Sarclisa) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) in patients with newly diagnosed multiple myeloma who are transplant ineligible.

VRd has been well-established standard of care in patients with newly diagnosed multiple myeloma, Facon began. However, the phase 3 IMROZ trial (NCT03310667) took a step further to evaluate the addition of isatuximab to VRd, he noted. The study population included patients who were older—a group with an unmet medical need, Facon emphasized. Of note, the study enrolled patients with multiple myeloma based on International Myeloma Working Group (IMWG) criteria who were 18 to 80 years of age with newly diagnosed disease and ineligible for transplant because of age (65 years or older) or comorbidities for those younger than 65 years of age.

Notably, the FDA approved Isa-VRd in September 2024 for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. The regulatory decision was supported by data from IMROZ. Findings, which were also published in The New England Journal of Medicine, revealed that Isa-VRd reduced the risk of disease progression or death by 40.4% vs VRd alone (HR, 0.596; 98.5% CI, 0.406-0.876; P < .001).

The study randomly assigned patients to receive either Isa-VRd (intravenous [IV] isatuximab plus subcutaneous bortezomib and oral lenalidomide with IV or oral dexamethasone) as induction treatment for 4 total 6-week cycles, then as continuous treatment in 4-week cycles, or VRd alone. During the continuous treatment phase, patients in the control arm who experienced disease progression were allowed to cross over to receive isatuximab plus Rd.

The primary end point of the study was progression-free survival. Secondary end points included complete response (CR) rate, minimal residual disease negativity rate among those who achieved CRs, very good partial response, overall survival, overall response rate, time to progression, duration of response, time to first response, and time to best response.