Amyloid-Targeting Antibody Elicits Organ Responses in Patients With Amyloidosis

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IN PREVIOUSLY treated patients with amyloid light-chain (AL) amyloidosis, the chimeric fibril-reactive monoclonal antibody 11-1F4 (CAEL-101) produced organ responses in about two-thirds of patients in a phase Ia/b trial reported at the 2017 American Society of Hematology (ASH) Annual Meeting & Exposition by Suzanne Lentzsch, MD, PhD, of Columbia University Medical Center, New York.

Suzanne Lentzsch, MD, PhD

Suzanne Lentzsch, MD, PhD

AL amyloidosis has a poor prognosis, with median survival varying from 12 to 18 months, depending largely on the severity of organ involvement. Current treatments focusing on eliminating the plasma cell clone that produces amyloidogenic light chains have improved overall survival, but the risk of early mortality remains high due to multiorgan dysfunction caused by persistent, insoluble amyloid fibril deposits, shared Dr. Lentzsch. 

“Amyloid fibril-reactive monoclonal antibody 11-1F4 was designed to target amyloid deposits by directly binding to a conformational epitope present on human light-chain amyloid fibrils,” Dr. Lentzsch explained. 

The antibody has been tested in mice with induced human AL amyloidosis, showing rapid destruction of amyloid fibrils without evidence of toxicity. Confirmation of the drug’s specificity for amyloid fibrils was further demonstrated on imaging studies in humans. 

“These promising results led to the development of GMP-grade [good manufacturing practice-grade] amyloid fibril-reactive chimeric immunoglobulin G1 monoclonal antibody 11-1F4 [CAEL-101] by the National Cancer Institute’s Biological Resource Branch,” she said. 

Final Analysis 

DR. LENTZSCH presented the final analysis of 11-1F4 in patients with AL amyloidosis previously treated with anti–plasma cell therapy enrolled in an open-label, dose-escalation phase Ia/b study. Patients received 11-1F4 as a single intravenous infusion (phase Ia) or a series of weekly infusions for 4 weeks (phase Ib). A dose-escalation “up and down” design was used for both phases, where successive doses of 0.5, 5, 10, 50, 100, 250, and 500 mg/m2 were administered. Researchers aimed to determine the maximum tolerated dose and to evaluate the safety and tolerability of the antibody. Secondary objectives included determination of pharmacokinetics and organ response. 


  • The investigational monoclonal antibody 11-1F4 (CAEL-101) was evaluated in a phase Ib/a study involving 27 patients with relapsed AL amyloidosis.
  • The drug directly targets the amyloid deposits in organs.
  • Treatment led to rapid and robust organ responses in about two-thirds of patients and was well tolerated.

Treatment was completed by 27 patients, including 8 in phase Ia and 19 in phase Ib, with 26 patients evaluable for response. All patients tolerated the given dose of the drug, up to the highest dose level of 500 mg/m2 in both phases. No drug-related grade 4 or 5 adverse events or dose-limiting toxicities were observed. 

Five patients (19%) developed a mild rash several days after infusion, which the investigators consider evidence that the 11-1F4 antibody directly binds to light-chain amyloid fibrils. Diarrhea and pain were also observed in five patients each, and elevated liver enzyme levels were reported in four patients. All of these side effects were grade 1/2. The maximum tolerated dose was determined to be 500 mg/m2

Rapid Organ Response 

AMONG 24 PATIENTS evaluable for response, 15 (63%) showed an organ response to treatment during the phase Ia/b trial. Eighteen patients had cardiac and/or renal involvement, and 12 of them (67%) showed a response to the drug. Three patients with other forms of organ involvement also responded to treatment, including one of four patients with gastrointestinal involvement, one of two patients with liver involvement, and one patient with soft-tissue response and improvement of arthritis from grade 3 to grade 1, Dr. Lentzsch reported. 

The median time to response was 3 weeks after the start of treatment, with the tendency toward quicker responses with higher dosages. Organ responses were independent of the free light chain type. 

“One of the biggest findings was you can achieve a response even with free light chains present,” she said. “But we saw that four treatments is not enough. Patients need more to break down the amyloid.” 

Elaborating on the cardiac response, Dr. Lentzsch reported that 6 of 12 patients (mean baseline NT-proBNP [N-terminal probrain natriuretic peptide] was ≥ 650 pg/mL) had a response, defined as > 30% and > 300 pg/mL decrease in baseline NT-proBNP, and 4 patients remained stable. The median time to cardiac response was 3 weeks. The drug improved left ventricular global longitudinal strain, as indicated in one patient whose baseline global longitudinal strain was –9.58 and NT-proBNP was 2,549 pg/mL but improved by week 12 to –13.39 global longitudinal strain and 1,485 pg/mL NT-proBNP. 

“An increase of global longitudinal strain by –2 is something that is significant,” she noted. “We saw improved contractility of the left ventricle.” 

Randomized Trials Planned 

“OVERALL, AMYLOID fibril–targeted therapy with the monoclonal antibody 11-1F4 represents both a promising and innovative approach to the management of patients with AL amyloidosis,” Dr. Lentzsch commented. “We postulate that in patients with persistent organ dysfunction after plasma cell–directed therapy, 11-1F4 leads to fast, early, and sustained organ response. The rapid destruction of amyloid fibrils by 11-1F4 can improve organ function and potentially improve mortality in patients with this uniformly fatal disease.” 

Larger randomized trials to evaluate the efficacy of this monoclonal antibody are planned, including trials of the drug in combination with anti–plasma cell therapy. ■

DISCLOSURE: Dr. Lentzsch reported financial relationships with Caelum Biosciences, Bayer, and Janssen. 


1. Edwards CV, Gould J, Langer AL, et al: Final analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with relapsed or refractory AL amyloidosis. 2017 ASH Annual Meeting. Abstract 509. Presented December 10, 2017. 

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