Modified High Dose Versus High Dose Melphalan Conditioning in Older Patients Undergoing Autologous Stem Cell Transplantation for Immunoglobulin Light Chain Amyloidosis

Introduction: High dose melphalan and autologous stem cell transplantation (HDM/SCT) results in deep and durable responses and prolonged survival in highly selected patients with systemic immunoglobulin light chain (AL) amyloidosis. HDM/SCT is offered to select patients >65 years but melphalan dose is often reduced due to concerns for tolerability and toxicities in older patients. However, older adults are a diverse population and chronological age alone does not accurately predict chemotherapy tolerance. While both melphalan 140 mg/m2 (MEL-140) and 200 mg/m2 (MEL-200) are commonly used in clinical practice, there are very few studies comparing these two doses in older patients. Available studies suggest that MEL-140 may be associated with worse event-free survival and progression-free survival, but it is unclear whether this is confounding for increased co-morbidities and frailty in this group. We report transplant-related toxicities and outcomes in patients >65 years undergoing first HDM/SCT with MEL-140 versus MEL-200 within 12 months of diagnosis of AL amyloidosis. Methods: We analyzed transplant-related toxicities and outcomes of patients >65 years who received first HDM/SCT within 12 months of diagnosis between January 2011 and June 2020. We excluded patients receiving additional conditioning agents and those undergoing tandem or second transplantation. Patients were stratified based on melphalan dose. All statistical analyses were performed using GraphPad Prism version 8©. Independent (unpaired) t tests with unequal variance and a 95% confidence interval were used to calculate the two-tailed p values for continuous variables. Chi-squared tests were used to compare categorical variables. Hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI) and p values are reported. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) and log-rank tests were used to compare the survival measurements of each group. In this cohort, PFS was defined as the time from SCT to hematologic progression, next line of therapy and/ or death, whichever came first. Transplant-related mortality was defined as death occurring within 100 days of SCT. Results: Forty patients were included in the final analysis with a median follow up of 55.0 months (range 7 - 109, n = 18) for surviving patients in both groups. Table 1 displays patient and disease characteristics, transplant-related toxicities, 2-year PFS and median