Isatuximab Approved First-Line for Transplant-Ineligible MM

The Food and Drug Administration expanded the label of isatuximab-irfc (Sarclisa — Sanofi-Aventis) on September 20 to include treatment with bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma (MM) ineligible for autologous stem cell transplant.

The new first-line indication joins two previous approvals of the CD38 antibody for later-line indications, one for relapsed disease with carfilzomib and dexamethasone, the other with pomalidomide and dexamethasone after at least 2 prior regimens that include lenalidomide and a proteasome inhibitor.

In addition to other MM indications, Isatuximab’s anti-CD38 competitor on the US market, daratumumab (Darzalex — Johnson & Johnson), also carries a first-line indication for transplant-ineligible MM in combination with either lenalidomide and dexamethasone or bortezomib, melphalan, and prednisone.

Isatuximab’s new approval is based on the open-label IMROZ trial in 446 patients randomized 3:2 to either isatuximab or placebo on a background of bortezomib, lenalidomide, and dexamethasone.

At a median follow-up of 59.7 months, estimated progression-free survival (PFS) was 63.2% with isatuximab add-on vs 45.2% in the placebo arm. Median PFS was not reached in the isatuximab group but 54.3 months with placebo (hazard ratio, 0.60; 98.5% CI, 0.41-0.88; P < .001). 

In a press release announcing the results, Sanofi said “IMROZ is the first global phase 3 study of an anti-CD38 monoclonal antibody” to show benefit in combination with bortezomib, lenalidomide, and dexamethasone, the current standard of care for transplant-ineligible MM.

Upper respiratory tract infections, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia, and COVID-19 were the most common adverse events in the isatuximab arm of IMROZ, occurring in 20% or more of subjects.

Eleven percent of isatuximab patients died during treatment vs 5.5% in the placebo group, driven primarily by infections.

The recommended dose of isatuximab is 10 mg/kg every week for 4 weeks followed by every 2 weeks until disease progression or unacceptable toxicity.

The cost is approximately $843 for 5 mL of the 20 mg/mL intravenous solution, according to Drugs.com.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.