AL Amyloidosis: The Prognostic Impact of Maintenance Therapy Following ASCT

Abstract

Introduction Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic AL amyloidosis (AL). However, the decision to utilize maintenance therapy following ASCT remains controversial and largely unexplored. Furthermore, the growing relevance of cytogenetics in AL may help dictate this maintenance decision as well. It is also relevant to note the emergence of novel targeted therapy options for AL patients, including the plasma cell monoclonal antibody daratumumab, that offer an exciting option in combination therapies with ASCT. As such, the present study aims to a) determine the prognostic significance of utilizing maintenance therapy following ASCT b) assess the potential impact of cytogenetics on this decision, and c) present novel data on the survival benefits of daratumumab-treated patients who have undergone ASCT. Methods A retrospective chart review was performed on 50 consecutive AL patients who underwent ASCT at The Ohio State University. Patients received high dose Melphalan (140 or 200 mg/m2) prior to ASCT. Patients were divided into subgroups based on FISH, and whether or not they had received maintenance therapy following transplant. Primary endpoints were progression free survival (PFS) and overall survival (OS), both estimated via the Kaplan-Meier survival function. The log-rank test was used to test the equality of survivor functions between different groups of patients. Results Twenty-eight patients (56%) received maintenance and 22 (44%) did not. There was no difference in age, dose of melphalan used, disease stage and number of organs involved between the two groups. There was no statistically significant difference in OS (p=0.32) and PFS (p=0.66) between patients who received maintenance versus those patients who did not receive maintenance (Figure 1A). Among patients with abnormal FISH, there was no difference in survival between the two groups (OS-p=0.65; PFS-p=0.15) (Figure 1B). Patients with three or more organs with AL involvement had worse OS/PFS versus those with 2 or less (OS-p=0.001; PFS-p=0.015). However, among these patients with 2 or more organs involved, the decision to utilize maintenance vs not showed no difference in PFS/OS. Lastly, further evaluation of a subset of patients treated with daratumumab showed no difference in outcome whether or not they underwent ASCT or consolidation. Conclusion In this small retrospective analysis, maintenance therapy post ASCT had no impact on the PFS or OS of patients with AL, even when further stratified based on degree of organ involvement. Survival was also not affected by cytogenetic abnormalities or with addition of novel monoclonal-targeted therapies. It is clear that a larger prospective study is needed to assess the benefit of maintenance post ASCT in AL amyloid patients.