P-009: Assessing the predictive utility of hematologic response for overall survival in patients with newly diagnosed AL amyloidosis: a systematic literature review and meta-analysis

Background Amyloid light-chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits made up of toxic light chains causing organ dysfunction and death. Prompt treatment is crucial to achieve deep hematologic responses, reverse organ damage, and improve overall survival (OS). Recent published studies suggest that hematologic response may be an important predictor of OS in AL amyloidosis. Here, we report the results of a meta-analysis evaluating the association between hematologic complete response (CR) and OS and very good partial response or better (≥VGPR) and OS in patients with newly diagnosed AL amyloidosis. Methods A systematic literature review (SLR) was conducted in November 2020 to identify all randomized controlled trials (RCTs) and comparative observational studies in patients with newly diagnosed AL amyloidosis. Databases were searched for articles published in English in August 2005 or later. Quality assessments were conducted and a feasibility assessment identified studies to include in the meta-analysis. Studies that reported OS hazard ratios (HRs) stratified by hematologic response were included in the analysis. If HRs were not reported, survival curves were digitized, and individual survival and censoring times were reconstructed using an algorithm by Guyot (2012). For curves with missing at-risk patient numbers, individual data were reconstructed manually. Heterogeneity was assessed using the I2 test and a random effects model was used. Statistical analysis was performed using STATA v16.1. Results The SLR yielded a total of 52 studies (4 RCTs and 48 observational studies). Eight of the 52 studies reported data on hematologic response and OS and were eligible for inclusion in the meta-analysis; of these, 5 reported OS stratified by hematologic CR status and 3 reported OS stratified by ≥VGPR status. The meta-analysis showed that achieving hematologic CR was associated with improved OS (HR, 0.18; 95% confidence interval [CI] 0.13–0.25). The I2 statistic was 0%, indicating a high degree of consistency across studies and that the heterogeneity observed across studies could be explained by sampling variability alone. Achieving ≥VGPR was also associated with improved OS (HR 0.16; 95% CI 0.09–0.28; I2 0%). Conclusion The meta-analysis revealed that in patients with newly diagnosed AL amyloidosis, achieving hematologic CR or ≥VGPR was associated with significantly improved OS and substantially decreased the risk of death. Potential limitations include the small number of RCTs (consistent with the rarity of the disease) and inconsistent reporting of results. Overall, these results support the use of deep hematologic response (CR or ≥VGPR) as an endpoint in studies of treatment for patients with newly diagnosed AL amyloidosis. Structured data collection of depth of response in future RCTs will further strengthen these observations.