Efficacy of Chemotherapy for Light-Chain Amyloidosis in Patients Presenting With Symptomatic Heart Failure

• Published in: Journal of the American College of Cardiology Vol. 67; no. 25; pp. 2941 - 2948
• Main Authors: Sperry, Brett W., MD, Ikram, Asad, MD, Hachamovitch, Rory, MD, Valent, Jason, MD, Vranian, Michael N., MD, Phelan, Dermot, MD, PhD, Hanna, Mazen, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.06.2016; Elsevier Limited
• Subjects: Aged; Alkylating Agents - therapeutic use; Amyloidosis - complications; Amyloidosis - drug therapy; Bone marrow; bortezomib; Bortezomib - therapeutic use; Cardiology; Cardiomyopathy; Cardiovascular; Cardiovascular disease; Confidence intervals; congestive heart failure; Coronary vessels; cyclophosphamide; Dexamethasone - therapeutic use; Drug Therapy, Combination; Electronic health records; Female; Heart Diseases - complications; Heart Diseases - drug therapy; Heart failure; Heart Failure - diagnosis; Heart Failure - etiology; Heart Failure - mortality; Humans; Immunoglobulins; infiltrative cardiomyopathy; Internal Medicine; Laboratories; Light; light chain; Male; Measurement techniques; Medical prognosis; Medical records; melphalan; Middle Aged; Mortality; Multiple myeloma; NMR; Nuclear magnetic resonance; Response rates; Retrospective Studies; Survival Rate; Treatment Outcome; infiltrative cardiomyopathy; NYHA; immunoglobulin light chain; OR; melphalan; CI; LV; AL; odds ratio; LVAD; free light-chain difference; New York Heart Association; NT-proBNP; bortezomib, dexamethasone, and alkylating agent; dFLC; light chain; congestive heart failure; cyclophosphamide; confidence interval; left ventricle/ventricular; left ventricular assist device; bortezomib; BDex+AA; N-terminal pro–B-type natriuretic peptide
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2016.03.593

Abstract Background Light-chain amyloidosis (AL) with cardiac involvement carries a poor prognosis; median untreated survival is <6 months. Three-drug therapy with bortezomib, dexamethasone, and an alkylating agent (BDex+AA) is associated with improved biomarker response rates in AL amyloidosis. Objectives This study sought to evaluate the effect of BDex+AA as a first-line treatment strategy on mortality in patients with symptomatic heart failure from AL cardiac amyloidosis. Methods Patients newly diagnosed with symptomatic New York Heart Association (NYHA) functional class ≥II heart failure due to AL amyloidosis were retrospectively studied. Initial treatment strategy was adjudicated and propensity score analysis was used to adjust for the nonrandomized allocation of treatments. Survival was assessed using a Cox proportional hazards model after adjusting for the propensity score for receiving treatment, age, NYHA functional class, and ejection fraction. Results Among 106 treated patients (age 64.6 ± 11.3 years, 63% male, 76% lambda subtype), 40 received the 3-drug regimen and 66 received other regimens. Mortality was 65% overall, 48% in the BDex+AA cohort (median survival time 821 days), and 76% in patients who received other regimens (median survival time 223 days). Initial treatment with BDex+AA was associated with decreased mortality after multivariable adjustment (hazard ratio: 0.209; 95% confidence interval: 0.069 to 0.636; p = 0.006). This association remained after further adjustment for components of the Mayo Stage. Conclusions Use of BDex+AA in the treatment of AL amyloidosis in patients presenting with symptomatic heart failure is associated with improved survival after adjusting for clinical variables.