FDA Approves Addition of Isatuximab to SOC for Relapsed/Refractory Multiple Myeloma

The FDA approved the addition of isatuximab (Sarclisa) to the combination of carfilzomib (Kyprolis) and dexamethasone (Kd) to treat adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, according to Sanofi, the agent’s manufacturer.

The treatment of this patient population has remained a challenge due to the disease’s poor prognosis, according to Peter C. Adamson, MD Global Development Head, Oncology and Pediatric Innovation, Sanofi. “With this approval, Sarclisa is now included in two standard of care regimens for the treatment of patients with multiple myeloma as early as first relapse. Today’s milestone further supports our ambition for Sarclisa to become the anti-CD38 of choice for patients with relapsed or refractory multiple myeloma,” he said in a press release.

The agency based its approval on data from the randomized, multicenter, open-label phase 3 IKEMA trial (NCT03275285), which showed that the triplet reduced the risk of disease progression or death by 45% vs Kd alone in this patient population (HR, 0.548; 95% CI, 0.366-0.822; P = .0032). At the time of the preplanned interim analysis, the median progression-free survival had not yet been reached with the isatuximab combination.

Additionally, no statistically significant difference in objective response rate was observed with the triplet vs the doublet, at 86.6% vs 82.9%, respectively (P = .03859); complete response rates were 39.7% vs 27.6%, respectively, and very good partial response rates were 33.0% and 28.5%, respectively. At the time of the interim analysis, data for overall survival were still immature.

The most common adverse events (AEs) in the combination and standard of care were upper respiratory tract infection (67% versus 57%, respectively), infusion-related reactions (46% versus 3.3%), fatigue (42% versus 32%), hypertension (37% versus 32%), diarrhea (36% versus 29%), pneumonia (36% versus 30%), dyspnea (29% versus 24%), bronchitis (24% versus 13%), and cough (23% versus 15%). Serious AEs in the isatuximab combination therapy arm 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%,” Dr. Thomas G. Martin, associate director of the Myeloma Program at The University of California, San Francisco, and professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program and co-leader of the Hematopoietic Malignancies Program at the Helen Diller Family Comprehensive Cancer Center, said in the 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,” he added.

Of note, this is the second approval for isatuximab, which is also approved in combination with pomalidomide and dexamethasone to treat adult patients with relapsed or refractory multiple myeloma who have received at least two prior therapies including lenalidomide (Revlimid) and a proteasome inhibitor.

Reference:

Sanofi News Release. 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.globenewswire.com/news-release/2021/03/31/2202919/0/en/FDA-approves-Sarclisa-isatuximab-in-combination-with-carfilzomib-and-dexamethasone-for-patients-with-relapsed-or-refractory-multiple-myeloma.html. Accessed March 31, 2021.