Graded Cardiac Response Correlates with Relapse and Survival in AL Amyloidosis

Seventy percent of all patients with light chain amyloidosis (AL) have cardiac involvement, and most of those patients ultimately die from complications related to their heart disease. While consensus guidelines outline criteria for grading hematologic response to chemotherapy for AL, there are no currently validated criteria for grading cardiac response to therapy. Recently, Muchtar et al. created a system for grading organ response, but excluded previously treated patients and those requiring multiple lines of therapy to achieve a response. Because the majority of AL patients receive multiple lines of therapy during their treatment course, we sought to validate cardiac grading criteria and demonstrate that they can be applied to a heterogeneous group of patients, including those who have been treated previously. Here we show how depth of best cardiac response at any point during a treatment course predicts both overall survival and risk of subsequent cardiac relapse defined as progression after an initial cardiac response. This is a retrospective cohort study of patients followed at the Stanford Amyloid Center with underling plasma cell dyscrasias causing biopsy-proven systemic AL involving the heart. Grading cardiac response involves categorizing the best response (the lowest NT-proBNP value) after initiation of treatment as either no response (NR), partial response (PR), very good partial response (VGPR), or complete response (CR). PR and VGPR are defined as a >30% and >60% reduction in NT-proBNP respectively; CR is defined as NT-proBNP 30% and >300 ng/L increase in NT-proBNP, whereas NR does not meet response criteria requiring a >30% and >300 ng/L reduction in NT-proBNP. Survival times were calculated from the time of first treatment to patient death or end of study (January 2018). Out of 252 patients with cardiac AL treated between June 2007 and January 2018, 114 had sufficient data for evaluation. Of those, 74 patients (65%) had cardiac responses to treatment, and 40 (35%) did not demonstrate a cardiac response. Of the responders, 60% had received more than one line of therapy by the time they achieved their best cardiac response. Kaplan Meyer survival analyses of patients grouped by cardiac response to therapy reveal that best depth of cardiac response to therapy at any point during the treatment course is predictive of overall survival by the log-rank test using a pre-treatment NT-proBNP assessment (p Our findings validate cardiac response grading as a useful tool for prognostication. Moreover, we demonstrate that cardiac response grading can be applied to patients who received several lines of therapy. This both increases the applicability of the tool and, in the context of CRs taking longer to achieve, demonstrates the clinical imperative to continue aggressive therapy in patients with suboptimal cardiac responses. Indeed, a CR or even VGPR achieved later in an illness trajectory has a demonstrated overall survival and cardiac progression free survival benefit. Disclosures Schrier:Forty Seven Inc.: Consultancy. Liedtke:Amgen/Onyx: Consultancy, Honoraria, Research Funding; BlueBirdBio: Research Funding; Takeda: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; celgene: Research Funding; Caelum: Membership on an entity9s Board of Directors or advisory committees; Prothena: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Gilead: Membership on an entity9s Board of Directors or advisory committees, Research Funding.