New first-in-class treatment for AL amyloidosis improves all-cause mortality

A phase 3 study of the investigational agent anselamimab showed a reduction in all-cause mortality and cardiovascular-related hospitalizations in patients with amyloid light chain (AL) amyloidosis when used in combination with standard of care chemotherapy. The benefit was specifically observed among patients with κ involved free light chain (iFLC) AL amyloidosis.

Ashutosh Wechalekar MD, of the National Amyloidosis Centre and University College London Hospitals, and colleagues presented the findings at the 2026 SOHO Annual Meeting.

Anselamimab is an investigational κ light chain-directed anti-fibril monoclonal antibody. In the CARES study, investigators assessed newly diagnosed patients with AL amyloidosis who were randomized 1:1 to receive anselamimab 1000 mg/m2 (n=271) or placebo (n=135) intravenously every seven days for four weeks, followed by every 14 days for the remainder of the study. Both groups also received cyclophosphamide, bortezomib, and dexamethasone; daratumumab was permitted and used in 79.3% of anselamimab- and 83.7% of placebo-treated patients.

The study included patients with European modification of Mayo stage 3a or 3b disease. Patients in both groups received treatment for a median of approximately 21 months. Subgroup analysis outcomes were assessed based on κ or λ iFLC.

Anselamimab-treated patients with κ iFLC saw a:

• 62% reduction in all-cause mortality (hazard ratio, 0.38; nominal P=0.012)
• 71% reduction in risk in cardiovascular hospitalizations (estimated rate ratio, 0.29; nominal P=0.028)

Patients with λ iFLC saw:

• A 10% reduction in risk in cardiovascular hospitalizations
• No reduction in all-cause mortality

Safety data were comparable between treatment groups, and in anselamimab-treated patients, safety findings were similar between the κ subgroup and overall population.

Reference

Wechalekar A, Dispenzieri A, Sanchorawala V, et al. Phase 3 randomized trial of anselamimab demonstrates improvement in all-cause mortality in κ light-chain amyloidosis. Abstract MM-218. Presented at the 2026 Society of Hematologic Oncology Annual Meeting; September 9-12, 2026; Houston.

Read more from SOHO 2026 here.