Impact of Age on Autologous Stem Cell Transplantation Outcomes for AL Amyloidosis

Introduction:

Consolidation with high-dose chemotherapy and autologous stem cell transplantation (ASCT) for patients with light chain amyloidosis (AL) is associated with deeper responses and improved outcomes. Several factors are known to be associated with worse outcomes. Older patients with AL frequently present with more advanced disease and have generally inferior outcomes compared to younger patients. In this study, we aimed to explore the impact of age on survival outcomes for AL patients who underwent ASCT at our institution.

Methods:

All consecutive patients with AL who underwent their first ASCT between 09/2005 and 11/2021, using a single agent melphalan conditioning regimen, were included. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included non-relapse mortality (NRM).

Results:

One-hundred-and-seventy-nine patients (109 males, 70 females) with a median age of 61 years (range, 27-77) were identified during the study period. Among these 102 (57%) were in the older age group (≥60 years) and 77 (43%) were in the younger age group (<60). Overall, there were no notable differences in baseline patient and disease characteristics between the two age groups, but a higher proportion of patients in the older group had an estimated glomerular filtration rate (eGFR) of <50 (31% vs. 19%, p=0.0765). With a median follow-up of 62 months (range 3.2-167.4), the 5-year PFS and OS for all study patients were 49% and 72%, respectively. The 5-year PFS for patients ≥60 was 44% compared to 55% for patients <60 (p=0.1022). The 5-year OS rate for patients ≥60 was 66% versus 80% for patients age <60 years (p=0.0081). The 1-year NRM was 11% for patients ≥60 compared to 2.6% for patients <60 (p=0.1246). Age and variables with p-value ≤0.15 in univariate analyses were included in multivariable analyses (MVA) for OS (HCT-Comorbidity Index, Beta-2 microglobulin, eGFR, Cardiac Involvement, Revised Mayo Staging). Age ≥60 (HR: 3.075; 95% CI: 1.374-6.884; p=0.0063) and Revised Mayo Stage III/IV (HR: 2.576, 95% CI: 1.145-5.796; p=0.0221) were significantly associated with inferior OS in MVA. In a subgroup analysis stratifying patients by their age and Revised Mayo Staging, patients age ≥60 with Mayo Stage III/IV had significantly inferior 5-year PFS/OS of 27%/37% vs 53%/77% vs. those in the same age group but with Mayo Stage I/II (p=0.02 for PFS; p=0.0012 for OS).

Conclusions:

For AL patients undergoing ASCT, our findings suggest that older patients with Mayo Stage I/II age have excellent long-term outcomes. Revised Mayo stage III/IV combined with age ≥60 years were predictive of poor outcomes, which warrants alternative treatment strategies for these patients.