Fecha de publicación: -- Fuente: PubMed "nature biotechnology" Eur J Cancer. 2026 Sep 10;248:117039. doi: 10.1016/j.ejca.2026.117039. Online ahead of print.ABSTRACTBACKGROUND: Light chain (AL) amyloidosis is a rare, potentially fatal plasma cell dyscrasia (PCD). Misfolded immunoglobulin light chains aggregate into amyloid fibrils, which deposit in organs. Current therapies suppress light chain overproduction but do not directly remove existing amyloid deposits. Anselamimab (CAEL-101) is an investigational monoclonal antibody designed to remove light chain amyloid fibrils. We evaluated its safety and tolerability combined with standard of care (SoC) anti-PCD therapy in participants with AL amyloidosis.METHODS: Adults with AL amyloidosis (European modification of Mayo 2004 stages I-IIIa) and measurable hematologic disease entered NCT04304144, a phase 2, multicentre, open-label, sequential-cohort, dose-selection study. Participants received 4 weekly anselamimab infusions (part A 500-1000 mg/m2; part B 1000 mg/m2) concurrent with SoC. Anselamimab was subsequently administered every 2 weeks until Week 50 and then optionally every 4 weeks until study end. Primary outcome was safety through 140 days post-treatment.RESULTS: Of 25 participants, 13 received anselamimab + CyBorD (cyclophosphamide, bortezomib, dexamethasone; Part A) and 12 received anselamimab + CyBorD + daratumumab (Part B). All participants experienced at least 1 treatment-emergent adverse event (TEAE), most mild-to-moderate. Sixteen participants (64.0%) experienced serious TEAEs. Four participants (16.0%) discontinued study drug because of TEAEs, and 3 participants (12.0%) experienced fatal TEAEs. All serious and fatal TEAEs were adjudicated as study-drug-unrelated. No dose-limiting toxicities occurred. Best cardiac responses occurred at Week 50 (47.4% of evaluable participants) and best renal responses at Weeks 62 and 98 (85.7% of evaluable participants).CONCLUSIONS: Anselamimab was well tolerated. Most common TEAEs were consistent with AL amyloidosis or anti-PCD therapy.PMID:42784867 | DOI:10.1016/j.ejca.2026.117039