Thierry Facon, MD, is a professor of hematology in the Department of Hematology at Lille University Hospital in France. 

Thierry Facon, MD, details the rationale for evaluating Isa-VRd in patients with transplant-ineligible, newly diagnosed multiple myeloma.

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.

 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 

, 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; 

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.

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Dr Facon on the Implications of Isatuximab Plus VRd in Transplant-Ineligible Newly Diagnosed Myeloma

Thierry Facon, MD, professor, hematology, Department of Hematology, Lille University Hospital, discusses the clinical implications from the phase 3 IMROZ trial (NCT03319667) investigating isatuximab-irfc (Sarclisa) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (Isa-VRd) in patients with transplant-ineligible, newly diagnosed multiple myeloma.

Facon highlights that during the trial, Isa-VRd demonstrated notable efficacy, particularly in terms of progression-free survival (PFS) improvements compared with VRd, suggesting that Isa-VRd has the potential to become a new standard of care for patients under 80 years of age with newly diagnosed multiple myeloma who are not candidates for autologous stem cell transplantation, which was the patient population enrolled on the study.

 showed a statistically improvement in PFS with Isa-VRd vs VRd along (HR, 0.596; 98.5% CI, 0.406-0.876; log-rank 

 = .0005). Isa-VRd (n = 265) led to a median PFS that was not reached (NR) vs 54.34 months (95% CI, 45.207-NR) for VRd alone (n = 181).

Beyond the improvement in PFS, Facon notes that Isa-VRd elicited deep responses, with improvements in complete response (CR) or better rate and minimal residual disease (MRD) negativity rates. The overall response rate was 91.3% for Isa-VRd vs 92.3% for VRd alone; however, the CR or better rate was 74.7% in the Isa-VRd arm vs 64.1% in the VRd arm.

In the intention-to-treat population, the MRD negativity rate was 58.1% for the Isa-VRd arm vs 43.6% for the VRd arm. The MRD-negative CR rates were 55.5% for Isa-VRd and 40.9% for VRd. MRD negativity was sustained for at least 12 months in 46.8% of patients in the ISA-VRd arm and 24.3% of patients in the VRd arm.

the FDA granted priority review to the supplemental biologics license application

 seeking the approval of Isa-VRd) for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma.

Thierry Facon, MD, discusses clinical implications from the phase 3 IMROZ trial

Thierry Facon, MD

Articles

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

Dr Facon on the Implications of Isatuximab Plus VRd in Transplant-Ineligible Newly Diagnosed Myeloma