Key Points

  • CAEL-101 is well tolerated in patients with AL amyloidosis.

  • CAEL-101 leads to rapid and sustained organ responses in patients with AL amyloidosis previously treated with standard therapy.

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by pathologic deposition of immunoglobulin light chains as amyloid fibrils in vital organs, leading to organ impairment and eventual death. That the process is reversible was evidenced in an in vivo experimental model in which fibril-reactive chimeric monoclonal antibody (mAb) 11-1F4 directly targeted human light-chain amyloid deposits and effected their removal via a phagocyte-mediated response. To determine tolerability and potential amyloidolytic effect of this agent (now designated mAb CAEL-101), we conducted a phase 1a/b study involving 27 patients, most of whom had manifestations of organ involvement. This was an open label study in which phase 1a patients received mAb CAEL-101 as a single intravenous infusion, with escalating dose levels from 0.5 mg/m2 to 500 mg/m2 to establish the maximum tolerated dose (MTD). In phase 1b, the antibody was administered as a graded series of four weekly infusions. For both phases, there were no drug-related serious adverse events or dose-limiting toxicities among recipients and the MTD was not reached. Majority of patients had deep hematologic responses but persistent organ disease prior to treatment. Fifteen of 24 patients (63%) who manifested cardiac, renal, hepatic, gastrointestinal, or soft tissue involvement had a therapeutic response to mAb CAEL-101 as evidenced by serum biomarkers or objective imaging modalities with median time to response of 3 weeks. Infusions of mAb CAEL-101 were well-tolerated and, for the majority, resulted in improved organ function, notably for those with cardiac impairment. This trial was registered at www.clinicaltrials.gov as NCT02245867.

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