Assessment of Treatment Response in Cardiac AL Amyloidosis Using CMR Mapping - Results at 3 Months, 6 Months and 1 Year Post-Chemotherapy

Introduction: Cardiac involvement in immunoglobulin light chain amyloidosis (AL) is the major determinant of survival. Cardiac response to chemotherapy is conventionally assessed by serum brain natriuretic peptide (NT-proBNP) and echocardiography, but neither quantify amyloid burden. Hypothesis: We assessed the hypothesis that CMR with T1 mapping and extracellular volume (ECV) can evaluate amyloid burden in cardiac AL amyloidosis tracking changes over time at 3 months, 6 months and 1 year after the initiation of chemotherapy. Methods: 94 patients with cardiac AL amyloidosis were studied serially using CMR with T1 mapping and ECV at baseline, 3 months, 6 months and 1 year post-chemotherapy. Results: At 6 months, 62% of patients achieved a complete response (CR) or very good partial haematological response (VGPR) to chemotherapy, and 38% a partial response (PR) or no response (NR). Amyloid regression was detectable in only 1 patient, however, there was amyloid progression in 34% of patients (Figure, panel A). Although this occurred in the PR group, it also occurred in the CR and VGPR groups (63%). At one year, 64% of patients achieved a good haematological response. Regression of amyloid was seen in 30% of patients (Figure, panel B), all with CR or VGPR and 0 patients in PR or NR (p<0.05). However, not every patient with CR or VGPR had amyloid regression by CMR, having 4 of these patients amyloid progression. Interestingly, these 4 patients achieved the good haematological response late (after the first 6 months of chemotherapy). 46% of patients with changes in ECV consistent with amyloid regression had also visual changes in the pattern of late gadolinium enhancement. Amyloid regression was associated with significant reduction in LV mass and NT-pro BNP (p<0.05) and in native T1 (p<0.01). Conclusion: In newly diagnosed and treated AL amyloidosis, CMR demonstrates the dynamic biology of infiltration: increasing rapidly, particularly if chemotherapy fails to switch off light chain production promptly; regressing more slowly (by one year) if effective. Serial monitoring of myocardial infiltration has the potential for new AL amyloidosis therapeutic regimes based on myocardial organ response.