OAB-038: Graded cardiac response criteria for AL amyloidosis: the impact of depth of cardiac response on survival

Abstract

<h3>Background</h3> Binary cardiac response assessment using NT-proBNP is prognostic in light chain (AL) amyloidosis. Previous studies suggested that refining the criteria to multi-level cardiac responses improves prognostic prediction. We aimed to validate a graded cardiac response assessment tool in AL amyloidosis using NT-proBNP or BNP. <h3>Methods</h3> In this retrospective, multicenter study AL amyloidosis patients who were diagnosed between 2010 and 2015, achieved at least a hematological partial response (PR) within 12 months of diagnosis and were evaluable for cardiac response (defined as baseline NT-proBNP >650 pg/mL or BNP >150 pg/mL) were included. The following response criteria were tested: cardiac complete response (carCR, nadir NT-proBNP≤350 pg/mL or BNP≤80 pg/mL); cardiac very good partial response (carVGPR, >60% reduction in NT-proBNP/BNP); Cardiac PR (carPR 31-60% reduction); and cardiac non response (carNR, ≤30% reduction). Response was assessed at fixed time points (6, 12 and 24 months from therapy initiation) and at best response. The primary outcome was overall survival based on depth of cardiac response. <h3>Results</h3> Six hundred and fifty-one patients were included. Mayo 2004 cardiac stage II, IIIA and IIIB was present in 47.5%, 38% and 14.5% of patients, respectively (by definition, patients with Mayo stage 1 do not have cardiac amyloidosis evaluable for response). Hematological CR, hematological VGPR and hematological PR was achieved in 38%, 39% and 23% of patients, respectively. Cardiac response improved over time with a median percentage reduction in NT-proBNP/BNP compared to baseline of 15%, 37% and 54%, at 6, 12 and 24 months respectively. At best cardiac response, carCR, carVGPR, carPR and carNR were achieved in 16%, 26%, 23% and 35% of patients, respectively. Patients achieving a carCR were more likely to be in cardiac stage II compared to carVGPR or carPR patients (65% vs 47% each, P30% rise in NT-proBNP/BNP) in multivariate analysis that included age, type of first line therapy, light chain burden, cardiac stage and hematological response. <h3>Conclusions</h3> We validated the prognostic value of graded cardiac response. These response criteria allow better discrimination of patient populations and assessment of treatment effectiveness in an era of improved therapies for AL amyloidosis. The study emphasizes the importance of early diagnosis which increases the likelihood of deep and durable cardiac responses.