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

J Am Coll Cardiol. 2016 Jun 28;67(25):2941-8. 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.

Keywords: bortezomib; congestive heart failure; cyclophosphamide; infiltrative cardiomyopathy; light chain; melphalan.

MeSH terms

  • Aged
  • Alkylating Agents / therapeutic use*
  • Amyloidosis / complications*
  • Amyloidosis / drug therapy*
  • Bortezomib / therapeutic use*
  • Dexamethasone / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Heart Diseases / complications*
  • Heart Diseases / drug therapy*
  • Heart Failure / diagnosis
  • Heart Failure / etiology*
  • Heart Failure / mortality*
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome

Substances

  • Alkylating Agents
  • Bortezomib
  • Dexamethasone