Kastritis Efstathios, Misra Arpit, Gurskyte Laura, Kroi Florint, Verhoek Andre, Vermeulen Jessica, Ammann Eric, Lam Annette, Cote Sarah, Wechalekar Ashutosh D
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
Cytel, Rotterdam, Netherlands.
Hematology. 2023 Dec;28(1):2157581. doi: 10.1080/16078454.2022.2157581.
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.
Studies were identified via systematic literature review. Pooled effect estimates were generated by a random-effects model.
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.
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.
淀粉样轻链（AL）淀粉样变性是一种罕见疾病，其特征是由毒性轻链组成的淀粉样纤维沉积物，可导致进行性器官功能障碍和死亡。最近的研究表明，血液学反应可能是AL淀粉样变性总体生存（OS）的重要预后指标。本研究的目的是评估新诊断患者血液学完全缓解（CR）或非常好的部分缓解或更好（≥VGPR）与OS之间的试验水平关联。
通过系统文献综述确定研究。采用随机效应模型生成合并效应估计值。
九项报告血液学CR或≥VGPR及OS风险比（HR）的观察性研究纳入荟萃分析。实现血液学CR与OS改善相关（HR，0.21；95%置信区间[CI]0.13 - 0.34）。实现≥VGPR也与OS改善相关（HR 0.21；95%CI 0.17 - 0.26）。排除一项离群研究的敏感性分析结果显示无异质性且总体HR估计更好。本荟萃分析的潜在局限性包括符合条件的研究数量少（与疾病的罕见性一致）以及结果报告不一致。
总体而言，我们的研究结果支持将深度血液学反应（CR或≥VGPR）用作新诊断AL淀粉样变性的临床试验终点。本研究提供了证据，表明早期血液学反应是接受一线治疗的AL淀粉样变性患者长期OS的有力患者水平替代指标。未来试验中对反应深度进行结构化数据收集将进一步加强这些观察结果。
