The investigational antifibril antibody anselamimab didn't clear the bar in its pivotal CARES trial for newly diagnosed advanced cardiac light-chain amyloidosis — but it wasn't a total washout. While the drug missed its primary composite endpoint of all-cause mortality and cardiovascular hospitalizations in the overall population, a prespecified subgroup analysis told a very different story for patients with kappa light-chain disease.

In the kappa subgroup, anselamimab delivered a 62% reduction in all-cause mortality (HR 0.38; P = .012) and a 71% reduction in cardiovascular hospitalization risk (rate ratio 0.29; P = .028) — numbers that researchers called potentially meaningful in a field with few fibril-clearing options. The lambda subgroup, which made up the majority of trial participants, saw no meaningful benefit.

By the Numbers

• Overall all-cause mortality HR: 0.80 (P = .290) — not significant
• Kappa subgroup mortality reduction: 62% (HR 0.38; P = .012)
• Kappa subgroup CV hospitalization reduction: 71% (rate ratio 0.29; P = .028)
• Lambda subgroup: no mortality benefit (HR 1.02); CV hospitalization reduction not significant
• Grade 3 adverse events: ~80–84% in both arms

Why it matters: Standard therapy (Dara-CyBorD) can eliminate the plasma cell clone producing toxic light chains, but it can't clear fibrils already lodged in the heart or kidneys. Anselamimab targets those existing fibrils — and for kappa patients, it may offer a meaningful survival edge. Experts stress that early initiation is critical, as survival curves didn't separate until 4–5 months in, by which point ~35% of the sickest patients had already died.