FDA Approval Insights: Isatuximab Plus Carfilzomib/Dexamethasone in Relapsed/Refractory Multiple Myeloma

Welcome to a very special edition of OncLive On Air^®! I’m your host today, Jessica Hergert.

OncLive On Air^® is a podcast from OncLive^®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive^® covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions. 

In today’s episode, we had the pleasure of speaking with Philippe Moreau, MD, a professor of clinical hematology, Nantes Faculty of Medicine, and head of the Translational Research Program at the University Hospital of Nantes, in Nantes, France, to discuss the FDA approval of isatuximab-irfc (Sarclisa) plus carfilzomib (Kyprolis) and dexamethasone (Kd) in relapsed/refractory multiple myeloma.

On March 31, 2021, the FDA approved isatuximab plus Kd for the treatment of patients with relapsed or refractory multiple myeloma who have previously received 1 to 3 lines of therapy.

The regulatory decision was based on findings from the phase 3 IKEMA trial (NCT03275285), in which 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 (PFS) was not reached with the triplet.

Of note, 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); the 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 immature.

The phase 3 trial enrolled 302 patients with relapsed/refractory myeloma who had received 1 to 3 prior lines of treatment. Eligible patients were randomized 3:2 to receive intravenous isatuximab at 10 mg/kg with Kd (n = 179) or Kd alone (n = 123).

Isatuximab was given on days 1, 8, 15, and 22 in cycle 1, and then every 2 weeks thereafter. Twice-weekly carfilzomib was administered at a dose of 20 mg/m² on days 1 and 2 and then at 56 mg/m² thereafter for 3 to 4 weeks. Dexamethasone was given at a twice-weekly dose of 20 mg. Treatment continued until progressive disease, intolerable toxicity, or the patient withdrawal.

Regarding baseline characteristics, the median age of patients was 64 years (range, 33-90), and 8.8% of were 75 years of age or older. The percentages of those with Revised Multiple Myeloma International Staging System I, II, and III disease were 53.2%, 30.2%, and 15.4%, respectively. Additionally, 44.4% of patients previously received 1 line of therapy, 32.5% had 2, and 21.4% had 3 or more. About 90% of patients (89.1%) had previously received a proteasome inhibitor, and 78.7% received a prior immunomodulatory drug; 33% of patients were refractory to lenalidomide (Revlimid). Twenty-four percent of patients had high-risk cytogenetics.

Regarding safety, the most common toxicities in the investigative arm vs the control arm included upper respiratory tract infection (67% vs 57%, respectively), 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 effects that were reported in more than 5% of patients who received the isatuximab triplet included pneumonia (25%) and upper respiratory tract infections (9%). Eight percent of patients who received the triplet permanently discontinued treatment because of toxicities; 2.8% of patients discontinued because of an infection.

In our exclusive interview, Moreau discussed the FDA approval of isatuximab-irfc plus carfilzomib and dexamethasone in relapsed/refractory multiple myeloma, key findings from the pivotal IKEMA trial, and future directions with the combination.