FDA Approves Isatuximab Plus Pomalidomide and Dexamethasone in Multiple Myeloma

The FDA has approved the combination of isatuximab-irfc with pomalidomide and dexamethasone as treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.

The FDA has approved the combination of isatuximab-irfc (Sarclisa) with pomalidomide and dexamethasone as treatment of adult patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide (Revlimid) and a proteasome inhibitor.

The approval is based on data from the ICARIA-MM study in which the combination demonstrated an improvement in progression-free survival (PFS) compared with pomalidomide and dexamethasone only. The median PFS observed was 11.53 months in the isatuximab group compared with 6.47 months with the pomalidomide-and-dexamethasone group (HR, 0.596; 95% CI, 0.44-0.81;P= .0010). The isatuximab combination also demonstrated a significantly higher overall response rate (ORR) of 60.4% compared with the 35.3% observed with pomalidomide and dexamethasone (P<.0001).

“Today’s FDA approval of Sarclisa provides a new treatment option for patients with difficult-to-treat multiple myeloma. These are patients whose disease has returned or become resistant to their prior treatments,” said Paul Hudson, chief executive officer, Sanofi. “Sarclisa offers a potential new standard of care in the United States. We continue to evaluate Sarclisa in a comprehensive clinical program in multiple myeloma, as well as in other blood cancers and solid tumors.”

The most common adverse events (AEs) observed with isatuximab were neutropenia (96%), infusion-related reactions (39%), pneumonia (31%), upper respiratory tract infection (57%) and diarrhea (26%), all of which occurred in >20% of patients in the experimental group. Serious AEs that occurred in >5% of patients and included pneumonia (25.3%) and febrile neutropenia (12.3%). Grade 3/4 AEs led to treatment discontinuation in 7% of the patients who were treated with isatuximab and 3% of the patients discontinued treatment due to an infusion-related reaction.

ICARIA-MM is a randomized, open-label, multicenter phase III study. The primary end point of the study is PFS, and the secondary end points included ORR, overall survival, time to progression, duration of response, and the number of participants with treatment-emergent adverse events.

In randomization, patients in the isatuximab arm received IV isatuximab 10 mg/kg on day 1, and then on days 1 and 15 of subsequent cycles combined with pomalidomide 4 mg on days 1 to 21 of each 28-day treatment cycle and IV dexamethasone 40 mg on day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant’s wish to discontinue study treatment, or any other reason, whichever comes first. Patients in the comparator arm received an equivalent dosage of pomalidomide plus dexamethasone.

Reference:

FDA approves Sarclisa&reg; (isatuximab-irfc) for patients with relapsed refractory multiple myeloma [news release]. Paris, France: Sanofi; March 2, 2020. https://bit.ly/2PGqszz . Accessed March 2, 2020.