Dr Bianchi on the Design of the CARES Trials of Anselamimab in AL Amyloidosis

“These [2] studies were designed to see whether adding anselamimab would affect all-cause mortality in treatment-naive patients with newly diagnosed light chain amyloidosis as they embarked on standard plasma cell–directed therapy. The question was whether adding this drug could reduce the early mortality signal seen in patients with advanced cardiomyopathy during the first 12 months following diagnosis.”

Giada Bianchi, MD, associate director of the Amyloidosis Program at Brigham and Women’s Hospital and Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School, discussed the design, treatment protocol, and eligibility criteria of the phase 3 CARES clinical program, comprising the CAEL 101-301 (NCT04504825) and CAEL 101-302 (NCT04512235) trials that evaluated the addition of anselamimab (CAEL-101) to standard plasma cell–directed therapy in patients with newly diagnosed light chain (AL) amyloidosis and advanced cardiac involvement.

Bianchi explained that the studies were designed to determine whether adding anselamimab could affect all-cause mortality (ACM) among treatment-naive patients beginning standard-of-care (SOC) therapy for the underlying plasma cell disorder. All enrolled patients received standard-of-care plasma cell–directed treatment consisting of cyclophosphamide, bortezomib (Velcade), and dexamethasone (CyBorD) with or without daratumumab (Darzalex). Patients were then randomly assigned 2:1 to receive either the investigational antibody anselamimab or placebo in addition to the SOC regimen.

The central question was whether directly targeting amyloid deposits with anselamimab could reduce ACM in patients with advanced amyloid cardiomyopathy, Bianchi said. This risk is particularly pronounced during the first 12 months following diagnosis, making early intervention an important focus of the CARES studies. The program included 2 parallel randomized, double-blind, placebo-controlled trials enrolling patients with Mayo stage IIIA (CAEL 101-301) or IIIB (CAEL 101-302) cardiac AL amyloidosis.

Bianchi added that the studies did not impose many additional major exclusion criteria. However, enrollment was limited specifically to patients with AL amyloidosis. Patients who also had a diagnosis of multiple myeloma were not contemplated for inclusion because the trials were intended to evaluate anselamimab in a clearly defined AL amyloidosis population receiving first-line plasma cell–directed therapy.

Importantly, the eligibility criteria permitted enrollment of patients with either kappa or lambda AL amyloidosis. Bianchi noteed that this inclusive approach was supported by preclinical research and early-phase clinical findings suggesting that anselamimab could provide benefit across both light chain isotypes. The trial design therefore allowed investigators to examine the agent’s potential impact across the broader advanced cardiac AL amyloidosis population.