Anselamimab’s Kappa Subgroup Signal Could Reshape Anti-Fibril Therapy in AL Amyloidosis

Anselamimab is a monoclonal antibody that binds to amyloid fibrils to speed their clearance, with the potential to enhance treatment in light chain (AL) amyloidosis, according to Meletios A. Dimopoulos, MD. In an interview with CancerNetwork®, at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting, Dimopoulos discussed where anti-fibril therapy may be heading in AL amyloidosis.

The investigational monoclonal antibody was evaluated in the phase 3 CARES program, which comprised 2 trials: one in Mayo stage IIIa disease (NCT04512235) and one in Mayo stage IIIb disease (NCT04504825). Across the program, 406 patients with newly diagnosed AL amyloidosis were randomly assigned 2:1 to receive anselamimab or placebo. Both arms also received cyclophosphamide, bortezomib (Velcade), and dexamethasone, with or without daratumumab (Darzalex). The program did not meet its primary end point, a hierarchical composite of all-cause mortality and cardiovascular hospitalizations, in the overall population (win ratio, 1.11; 95% CI, 0.83-1.50; P = .332).

In a prespecified subgroup of 72 patients with the kappa isotype, anselamimab reduced all-cause mortality by 62% vs placebo (HR, 0.38; 95% CI, 0.17-0.86; nominal P = .012). It also reduced cardiovascular hospitalizations by 71% (incidence rate ratio, 0.29; 95% CI, 0.10-0.87; nominal P = .028). No clinical benefit was observed in patients with lambda disease.

Dimopoulos is professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Greece.

Transcript:

CancerNetwork: Anselamimab’s kappa-specific subgroup result is generating real discussion in amyloidosis this year. How does that finding fit into your broader view of where anti-fibril therapy is heading relative to anti–plasma cell therapy?

Dimopoulos: In order to improve the outcome of patients with amyloidosis, for many years we have focused on regimens and treatment strategies that would rapidly reduce the production of the toxic light chains that are causing the amyloid deposits. However, in recent years, there have been attempts to increase the degradation of the already deposited amyloid. These anti-fibril amyloid therapies have been investigated, and so far we have a positive signal with this monoclonal antibody, which has been shown to be effective only in patients with kappa light chain amyloidosis, which represents about 20% of patients with AL amyloidosis. This is an important positive finding that gives us the opportunity to further investigate anti-fibril treatment strategies.

Reference

Wechalekar AD, Dispenzieri A, Sanchorawala V, et al. Efficacy and safety of anselamimab in immunoglobulin light chain amyloidosis: results from the randomized CARES trials. J Clin Oncol. 2026;44(20):1899-1910. doi:10.1200/JCO-26-00755