Isatuximab Granted FDA Approval for Relapsed, Refractory Multiple Myeloma

The FDA has approved isatuximab (Sarclisa, Sanofi) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma.

Multiple myeloma is the second most common hematologic malignancy, affecting more than 130,000 patients in the United States, according to a Sanofi press release. Despite some available treatments, it remains incurable and has significant patient burden. Most patients will relapse or become refractory when their cancer no longer responds to therapy.

This is the second FDA approval for isatuximab in combination with standard-of-care therapies, following its approval in March 2020 in combination with pomalidomide and dexamethasone for relapsed refractory multiple myeloma. Isatuximab is a monoclonal antibody that binds to an epitope on the CD38 receptor on multiple myeloma cells. It works through several mechanisms of action, including apoptosis and immunomodulatory activity, according to the press release.

“Treatment of patients with relapsed or refractory multiple myeloma remains challenging and the prognosis for patients experiencing multiple relapses unfortunately is poor,” said Peter C. Adamson, MD, global development head of Oncology and Pediatric Innovation at Sanofi, in the press release. “With this approval, Sarclisa is now included in 2 standard of care regimens for the treatment of patients with multiple myeloma as early as first relapse.”

The new approval is based on data from the phase 3 IKEMA study, which enrolled 302 patients with relapsed multiple myeloma across 69 centers in 16 countries. Demographic and disease characteristics at baseline were balanced between the combination treatment group and the standard-of-care group. The researchers noted that they enrolled a difficult-to-treat patient population, including those who are elderly, have high cytogenetic risk, or renal impairment.

According to the press release, investigators found that isatuximab in combination with carfilzomib and dexamethasone reduced the risk of disease progression or death by 45% versus standard of care alone. At the time of the pre-planned interim analysis, the researchers said the median progression-free survival had not yet been reached.

Secondary endpoints in the trial assessed the overall response rate (ORR), including complete response (CR) and very good partial response (VGPR). The researchers found no statistically significant difference in ORR, which was 86.6% for the isatuximab arm and 82.9% for the standard-of-care arm. The rate of CR was 39.7% in the isatuximab arm compared to 27.6% in the standard-of-care arm. Finally, the rate of VGPR was 33% for patients receiving isatuximab and 27.6% in the standard-of-care arm.

The most frequent adverse reactions for isatuximab versus the control arm were upper respiratory tract infection (67% vs. 57%), infusion-related reactions (46% vs. 3.3%), fatigue (42% vs. 32%), hypertension (37% vs. 32%), diarrhea (36% vs. 29%), pneumonia (36% vs. 30%), dyspnea (29% vs. 24%), bronchitis (24% vs. 13%), and cough (23% vs. 15%). Serious adverse reactions that occurred in more than 5% of patients who received the combination therapy were pneumonia (25%) and upper respiratory tract infections (9%).

“In the phase 3 IKEMA study, the addition of Sarclisa to carfilzomib and dexamethasone reduced risk of disease progression or death by 45%,” said Thomas G. Martin, MD, associate director of the Myeloma Program at the University of California, San Francisco, in the press release. “This approval is an important advancement for patients whose disease has relapsed and reinforces the potential for Sarclisa to become a standard of care in relapsed or refractory multiple myeloma.”

REFERENCE

FDA approves Sarclisa (isatuximab) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma [news release]. Sanofi; March 31, 2021. https://www.sanofi.com/en/media-room/press-releases/2021/2021-03-31-23-15-00-2202919#. Accessed April 1, 2021.