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Journal of Comparative Effectiveness... Jun 2024The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy... (Review)
Review
The six-minute walk test (6MWT) is a common measure of functional capacity in patients with heart failure (HF). Primary clinical study end points in cardiomyopathy (CM) trials, including transthyretin-mediated amyloidosis with CM (ATTR-CM), are often limited to hospitalization and mortality. To investigate the relationship between the 6MWT and hospitalization or mortality in CM, including ATTR-CM. A PRISMA-guided systematic literature review was conducted using search terms for CM, 6MWT, hospitalization and mortality. Forty-one studies were identified that reported 6MWT data and hospitalization or mortality data for patients with CM. The data suggest that a greater 6MWT distance is associated with a reduced risk of hospitalization or mortality in CM. The 6MWT is an accepted alternative end point in CM trials, including ATTR-CM.
PubMed: 38869839
DOI: 10.57264/cer-2023-0158 -
Amyloid : the International Journal of... 2019
Topics: Aged; Amyloidosis; Heart Failure; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Male; Nephrotic Syndrome
PubMed: 31343287
DOI: 10.1080/13506129.2019.1582022 -
Blood Advances Jul 2024
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Clinical Trials as Topic; Immunoglobulin Light Chains
PubMed: 38696707
DOI: 10.1182/bloodadvances.2024012737 -
Hematology (Amsterdam, Netherlands) Dec 2023Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing progressive organ dysfunction and death. Recent studies suggest that hematologic response may be an important prognostic indicator of overall survival (OS) in AL amyloidosis. The aim of this study was to evaluate the trial-level association between hematologic complete response (CR) or very good partial response or better (≥ VGPR) and OS in newly diagnosed patients.
METHODS
Studies were identified via systematic literature review. Pooled effect estimates were generated by a random-effects model.
RESULTS
Nine observational studies reporting hematologic CR or ≥VGPR and OS hazard ratios (HRs) were included in the meta-analysis. Achieving hematologic CR was associated with improved OS (HR, 0.21; 95% confidence interval [CI] 0.13-0.34). Achieving ≥ VGPR was also associated with improved OS (HR 0.21; 95% CI 0.17-0.26). Results of a sensitivity analysis excluding one outlier study revealed no heterogeneity and a better overall HR estimate. Potential limitations of this meta-analysis include the small number of eligible studies (consistent with the rarity of the disease) and inconsistencies in reporting of results.
CONCLUSIONS
Overall, our findings support the use of deep hematologic response (CR or ≥VGPR) as a clinical trial endpoint in newly diagnosed AL amyloidosis. This study provides evidence that early hematologic response is a strong patient-level surrogate for long-term OS in patients with AL amyloidosis receiving frontline therapy. Structured data collection of depth of response in future trials will further strengthen these observations.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Prognosis; Remission Induction; Proportional Hazards Models
PubMed: 36607151
DOI: 10.1080/16078454.2022.2157581