FDA Approves Isatuximab With Carfilzomib and Dexamethasone for Adults With R/R Multiple Myeloma


The FDA has granted approval to the combination of isatuximab added to carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.

The FDA has granted approval to the combination of isatuximab added to carfilzomib and dexamethasone (Kd) for the treatment of adult patients with relapsed or refractory (R/R) multiple myeloma who have received 1 to 3 prior lines of therapy, according to a press release from Sanofi.1

The triplet regimen received approval based on results from the phase 3 IKEMA clinical trial (NCT03275285) which showed prolongation in progression-free survival (PFS) compared with the current standard-of-care (SOC) of Kd in patients with RRMM, therefore meeting the study’s primary end point.

“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, said Thomas G. Martin, MD, associate director, Myeloma Program, The University of California, San Francisco, Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program and co-leader of the Hematopoietic Malignancies Program, Helen Diller Family Comprehensive Cancer Center.

IKEMA is a randomized, multi-center, open-label trial enrolling 302 patients with R/R multiple myeloma. Patients were treated across 69 centers in 16 different countries. Isatuximab is administered to patients at a dose of 10 mg/kg once weekly for 4 weeks, followed by every other week for a cycle of 28 days. Carfilzomib 20/56 mg/m2 was administered twice weekly, and dexamethasone was administered at the standard dose for the full length of therapy. The secondary end points investigated in the study included overall response rate (ORR), the rate of very good partial response (PR) or greater, minimal residual disease (MRD), complete response (CR) rate, overall survival (OS), and safety.

The study was open to patients with multiple myeloma that has been previously treated with 1 to 3 prior lines of therapy. Patients were required to have measurable disease in order to be eligible for enrollment. Those who received prior treatment with carfilzomib within 14 days of the start of the study were ineligible to be included in IKEMA. Patients were also ineligible for the study if they were under the age of 18 years old, had inadequate biological tests, myocardial infarction, previous cancer within in 5 years, and a known acquired immunodeficiency syndromes related illness.

In a previous interview with Targeted Oncology around the IKEMA trial results, study co-author, Phillipe Moreau, MD stated, “IKEMA met its primary end point with a significant reduction in the risk of progression or death. The benefit was absorbed across multiple subgroups of patients, including those difficult-to-treat subgroups. The responses were also higher in the isatuximab arm, and the safety profile was manageable with the triplet combination. We can think that this study will be considered for approval of isatuximab for R/R myeloma patients with 1-3 prior lines of treatment. This combination will potentially represent a new standard of care in this setting.”

With the isatuximab plus Kd, there was a 45% reduction in the risk of disease progression or death compared with Kd alone (HR, 0.548, 95% CI 0.366-0.822, P =.0032). Median PFS was not reached at the time of the pre-planned interim analysis, and OS data were immature.

In terms of the secondary trial end points, the ORR was 86.6% with isatuximab plus Kd versus 82.9% for Kd alone (P =.3859). The triplet combination arm also achieved a higher CR rate of 39.7% compared with the Kd arm, which had an ORR of rate 27.6% (P =.3859). In addition, there was a VGPR of 33% for patients who received the isatuximab triplet versus 28.5% for patients who received Kd.

According to a prior announcement, there were no new safety signals observed with the addition of isatuximab.2 Adverse events occurred in over 20% of patients, with the most common in the triplet arm versus the doublet arm being 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 AEs have also been observed with the triplet and the doublet, which were commonly pneumonia (25%) and upper respiratory tract infections (9%) occurring in more than 5% of patients.1

In the study, 8% of patients who received isatuximab plus Kd permanently discontinued treatment due to grade 1-4 AEs. Another 2.8% discontinued treatment as a result of an infection.


1. FDA approves Sarclisa® (isatuximab) in combination with carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma. News release. Sanofi. March 31, 2021. Accessed March 21, 2021. https://bit.ly/3sGgfo8

2. Sarclisa (isatuximab) phase 3 IKEMA trial meets primary endpoint early in patients with relapsed multiple myeloma. News release. Sanofi. May 12, 2020. Accessed May 12, 2020. https://bit.ly/2Ahe4Rr.

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