Clonal plasma cell features in light-chain amyloidosis are associated with depth and timing of cardiac response independent of hematologic response

Abstract

Cardiac response (CarR) is associated with survival in AL amyloidosis, but substantial variation exists in response kinetics. We investigated variables associated with deep CarRs to characterize the factors that govern organ recovery. Retrospective study of newly-diagnosed AL amyloidosis patients (n=401) diagnosed between 2010-2022 and assessable for CarR. CarRs were recorded at 6, 12, 24-months and the best CarR. Deep CarR was defined as CarVGPR or better (>60% reduction in baseline NT-proBNP or ≤350 pg/mL). High-risk cytogenetic abnormalities (HRCAs) included del(17p), t (4;14), t(14;16), and t(14;20). Logistic and competing-risk regression (treating death as a competing event) were used to examine variables associated with CarR. The median age was 65-years, with a median follow-up of 5.5-years. At 6, 12, 24-month and best overall response landmarks, 12%, 24%, 33% and 45% of patients had obtained ≥CarVGPR, respectively. Baseline bone-marrow plasma-cells (BMPCs) ≥20%, obtaining ≥hemVGPR within 6-months, kappa isotype, HRCAs and ASCT were significantly associated with deep CarR on logistic regression and competing-risk analysis. In-line with their impact on CarR, ASCT, kappa isotype and deep HemR within 6-months were associated with improved overall survival (OS) on multivariable Cox proportional hazards modeling. Conversely, high BMPC burden and the presence of HRCAs had no association with OS on adjusted analysis. As this cohort was retrospectively selected for CarR assessment, these results need to be interpreted accordingly. Nonetheless, the association between a ‘myeloma phenotype’ and CarR kinetics, endorses the role of direct light-chain toxicity and suggests that clonal plasma-cell features significantly influence organ response in AL amyloidosis.