Author + information
- Received February 8, 2019
- Revision received July 10, 2019
- Accepted July 11, 2019
- Published online October 9, 2019.
- Christopher D. Barrett, MD,
- Katharine Dobos, MD,
- Michaela Liedtke, MD,
- Mirela Tuzovic, MD,
- Francois Haddad, MD,
- Yukari Kobayashi, MD,
- Richard Lafayette, MD,
- Michael B. Fowler, MB,
- Sally Arai, MD,
- Stanley Schrier, MD and
- Ronald M. Witteles, MD∗ ()
- ↵∗Address for correspondence:
Dr. Ronald M. Witteles, Stanford Amyloid Center, Stanford University School of Medicine,300 Pasteur Drive, Lane Building #L158, Stanford, California 94305.
Objectives The purpose of this study was to address the overall trends in mortality since the adoption of modern therapies for treatment of systemic amyloidosis, and to reconsider the prognostic significance of individual components of the current staging system.
Background Systemic light chain (AL) amyloidosis involves deposition of immunoglobulin light chains in organs throughout the body and is known to have the highest mortality when significant cardiac involvement is present. Survival has historically been poor but may be improving as systemic therapies continue to advance. This study assesses whether recent advancements in light chain directed therapy have led to improved survival in patients with systemic AL amyloidosis.
Methods We reviewed all cases of patients who were evaluated for a new diagnosis of AL amyloidosis at the Stanford Amyloid Center between 2009 and 2016. Patients’ stage at diagnosis was determined according to the most commonly used staging system. Clinical data, overall survival from diagnosis, and the independent influence of each component of the staging system were analyzed.
Results At total of 194 patients were identified with a new diagnosis of systemic AL amyloidosis. Median overall survival was 59 months and 6 months for stage 3 and 4 patients, respectively. Median overall survival was not reached in stage 1 and 2 groups, as survival was >50% by the end of the study. Mean overall survival was 118 months, 76 months, 64 months, and 27 months in Stages 1, 2, 3, and 4 patients, respectively. Although N-terminal pro–B-type natriuretic peptide and troponin I concentrations had large effects on prognosis, differences in serum free light chains (dFLC) on initial staging laboratory results ≥18 mg/dl, part of the current staging system, did not contribute significantly to prognosis for values ≥5 mg/dl.
Conclusions Survival for patients with systemic AL amyloidosis has improved for patients at all stages of disease in the present era of rapid advancements in light chain-reducing therapies. Cardiac biomarkers at diagnosis, but not baseline dFLC ≥18 mg/dl, continue to provide important prognostic information.
Supported by the generosity of the Helen Diller Family Foundation Amyloid Research Fund.
Dr. Liedtke has received research support through her institution; and she has received personal fees from Celgene, Amgen/Onyx, Gilead, Pfizer, Prothena, Takeda, Caelum, Adaptive, and IQVIA/Jazz. Dr. Witteles is an advisory board member for Pfizer and Alnylam; and he has received research support from Pfizer, Alnylam, and Eidos. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 8, 2019.
- Revision received July 10, 2019.
- Accepted July 11, 2019.
- 2019 American College of Cardiology Foundation
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