Don Tracy, Associate Editor

Reportedly, data from the IMROZ study marks the first time an anti-CD38 monoclonal antibody combined with standard-of-care therapy has demonstrated significant improvement in progression-free survival for newly diagnosed transplant-ineligible multiple myeloma.
Results from the IMROZ Phase III trial show that Sanofi’s Sarclisa (isatuximab-irfc) in combination with standard-of-care therapy comprised of lenalidomide and dexamethasone (VRd) significantly reduced the risk of disease progression or death by 40% compared to a solo VRd regimen in patients with newly diagnosed transplant-ineligible multiple myeloma (MM). According to the company, the data represents the first time an anti-CD38 monoclonal antibody combined with VRdsupported a significant improvement in progression-free survival (PFS) for these patients.
“The significant progression-free survival (PFS) benefit observed with Sarclisa combination therapy compared to VRd is important and encouraging for patients with newly diagnosed multiple myeloma. Effective frontline therapy has the potential to modify the course of the disease, which is a key outcome for transplant-ineligible patients who often face high rates of attrition in later lines of therapy. The IMROZ results demonstrate the promise of Sarclisa as a backbone to frontline therapy, which may improve long-term outcomes for this incurable disease,” said IMROZ principal investigator Thierry Facon, MD, professor of hematology, department of hematology, Lille University Hospital, Lille, France, member of French Academy of Medicine, in a press release.
The global, randomized, multi-center, open-label IMROZ trial enrolled 446 patients with newly diagnosed, transplant-ineligible MM throughout 21 countries and 104 centers. The primary endpoint of the study was PFS, with secondary endpoints that include complete response (CR) rate, minimal residual disease (MRD) negativity rate for patients with a CR, significant partial response or better rate, and overall survival (OS).
The study found that the Sarclisa-VRd combination significantly reduced the risk of disease progression or death by 40%. Further, results demonstrated an estimated PFS of 63.2% for patients treated with Sarclisa-VRd at 60 months versus 45.2% for VRd. Data show that 74.7% of patients treated with Sarclisa-VRd achieved a CR compared to 64.1% treated with VRd, and 46.8% of patients treated with the combination achieved MRD for at least one year as opposed to 24.3% for patients taking VRd alone.
Regarding safety of the treatment, it remained consistent with previous analyses, and no new safety signals were reported. Treatment-emergent adverse events at grade ≥3 were discovered in 91.6% of patients taking Sarclisa-VRd and 84% of patients taking VRd, which led to treatment discontinuation in 22.8% of patients taking Sarclisa-VRd and 26% of patients taking VRd.
The trial data is expected to be presented at the European Hematology Association Annual Congress and was also featured during the American Society of Clinical Oncology (ASCO) best of ASCO program. Further, the FDA has granted priority review to the Biologics License Application for Sarclisa in combination with VRd, with another submission under review in the EU.1
“Over the last 20 years, the pace of multiple myeloma research has continued to accelerate, paving the way for treatment advancements with potential to improve outcomes for patients. With our commitment to help lead the way for patients with this disease, we welcomed the IMROZ results presented at ASCO, and now published in NEJM, which demonstrate Sarclisa’s potential to improve progression-free survival in patients who are newly diagnosed and transplant ineligible. We want to express our deep gratitude to the patients, their families and investigators for their dedication to clinical research,” said Peter C. Adamson, global development head, Oncology, Sanofi, in the press release.