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JACC March 8, 2022

Volume 79, Issue 9, suppl A

Heart Failure and Cardiomyopathies

SAFETY AND TOLERABILITY OF CAEL-101, AN ANTI-AMYLOID MONOCLONAL ANTIBODY, IN
COMBINATION WITH PLASMA CELL DYSCRASIA THERAPY IN PATIENTS WITH LIGHT-CHAIN
AMYLOIDOSIS: RESULTS FROM A PHASE 2 STUDY
Moderated Poster Contributions
Heart Failure and Cardiomyopathies Moderated Poster Theater 1_Hall C
Monday, April 4, 2022, 1:30 p.m.-1:40 p.m.

Session Title: Cardiac Amyloid: The Latest and Greatest

Abstract Category: 11. Heart Failure and Cardiomyopathies: Special Populations
Presentation Number: 1113-13

Authors: Jason Valent, Michaela Liedtke, Jeffrey Zonder, John Silowsky, Michael Kurman, Eileen Daniel, Janet Jobes, Mark Harnett, Amit
Bhattacharyya, Candida Cristina Quarta, Julia Catini, Jessica Raviwong, Michael Spector, Susan Sobolov, Alexion, AstraZeneca Rare
Disease, Bordentown, NJ, USA, Alexion, AstraZeneca Rare Disease, Boston, MA, USA
Background: Light-chain amyloidosis (AL) is a rare, systemic disease caused by plasma cell dyscrasia (PCD) that overproduces
immunoglobulin light chains, which misfold and aggregate to form amyloid fibrils. Fibrils deposit in organs, primarily the heart, with mortality
driven largely by heart involvement. Current treatments target PCD to halt fibril formation without addressing existing fibrils deposited in
organs. CAEL-101 is a novel, investigational, first-in-class therapy designed to remove amyloid fibrils from organs. The objective is to
analyze safety, tolerability, and effect on cardiac biomarkers of CAEL-101 given with CyBorD +/- daratumumab.
Methods: Adult patients with AL (Mayo Stage I-IIIa) and measurable hematologic disease were eligible for this ongoing, open-label, phase
2 study (NCT04304144). Other forms of amyloidosis and multiple myeloma were excluded. Patients are receiving CAEL-101 ≤1000 mg/m2
every other week with anti-PCD therapy. In addition to safety assessments, cardiac response was assessed by change over time in cardiac
troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP).
Results: Patients (n = 25; mean age 65 y; 72% male) with Mayo Stage I (8%), II (76%), and IIIa (16%) AL received CAEL-101 for 344
days (median). Patients presented with cardiac involvement (n = 20), renal involvement (n = 8), and prior anti-PCD therapy (n = 20). In
all, 24 patients experienced treatment-emergent adverse events (TEAE), but only 6 experienced treatment-related TEAE. Three patients
discontinued for non-treatment-related reasons. The most common TEAEs were nausea (n = 9), constipation (n = 8), and diarrhea,
fatigue, or rash (n = 7 each). Cardiac TEAEs occurred in 6 patients, all unrelated to CAEL-101. Of 20 cardiac-evaluable patients, 30%
were responding (≥30% NT-proBNP improvement from baseline) and 60% were stable (±30% change from baseline) at their most recent
assessment.
Conclusion: The long-term safety evaluation of CAEL-101 continues in this study. To date, CAEL-101 is well tolerated without evidence
of cardiac toxicity. Cardiac responses were observed. A phase 3 program is ongoing to elucidate the efficacy and safety of CAEL-101 in
cardiac AL.