Single-Center Retrospective Analysis of Autologous Stem Cell Transplantation for Patients with Systemic Light Chain Amyloidosis

Introduction

AL (Amyloid Light chain) amyloidosis is a rare disease characterized by the misfolding and aggregation of light chain from monoclonal immunoglobulins into amyloid deposits. These deposits are associated with monoclonal plasma cell, leading to organ dysfunction. Current therapeutic strategies focus on eliminating monoclonal plasma cell neoplasms. High-dose melphalan and autologous stem cell transplantation (HDM/SCT) for patients with AL amyloidosis has been employed, but the eligibility criteria for HDM/SCT have been tightened because of the significantly higher mortality rate due to organ dysfunction and decreased Performance status. Furthermore, with the recent advent of anti-CD38 antibodies, the significance of HDM/SCT has been reexamined and the role of HDM/SCT in the treatment paradigm of transplant-eligible patients with AL amyloidosis is not sufficient evidences. This retrospective study aims to determine the prognosis of AL amyloidosis patients who underwent HDM/SCT in our hospital.

Methods

This retrospective, non-interventional cohort study includes data from the electronic medical records of AL amyloidosis patients treated at the Japanese Red Cross Medical Center (JRCMC). The study was approved by the JRCMC Institutional Review Board and conducted under an informed consent procedure with an opt-out option. Overall survival (OS) was defined as the time between the first day of HDM/SCT (day 0) and date of death from any cause or last follow-up. Treatment-related mortality (TRM) was defined as death from any cause between day 0 and day +100. Treatment efficacy was evaluated at 3 months after transplantation. Comparisons of categorical variables were made using the Chi-square test or Fisher test depending on the number of observations. Comparisons of continuous variables were made with the Mann Whitney U Test. The outcome measure was odds ratio (OR) with a 95% confidence interval (CI). OS was calculated using the Kaplan–Meier method and estimates between groups were compared by the log-rank test. The Cox-proportional hazard regression method was used to fit univariable and multivariable models for OS; the outcome measure was hazard ratio (HR) with 95% CI. p-values <.05 were considered statistically significant. All calculations were obtained using the EZR software version 4.33.

Results

The study included 121 patients with systemic AL amyloidosis who underwent HDM/SCT from June 2006 to December 2023. The median age was 57 years (range: 32–70 years) and 63 patients (51.2%) were male. The distribution of free light chain types was 98 patients (81.0%) with lambda chains. Organ involvement included the cardiac involvement in 40 patients (33.1%), renal involvement in 88 patients (72.7%), gastrointestinal tract involvement in 44 patients (36.4%), and liver involvement in 25 patients (20.7%). Organ response rates were 76.9% for cardiac involvement, 76.5% for renal involvement, and 54.2% for liver involvement. The median follow-up duration was 56.44 months (range: 0.26–185.45 months). The median overall survival was not reached (95% CI, 12.54 years–not reached [NR]), with a 10-year overall survival rate of 69.2% (95% CI, 56.2–79.1%). Since 2021, there have been no TRM among 21 patients. The overall hematologic response rate was 94% (84/89 patients), with complete response in 52 patients (58.4%), very good partial response in 16 patients (18.0%), and partial response in 16 patients (18.0%). Univariate analysis indicated that cardiac involvement, lower dose (< 200 mg/m²) of melphalan, revised Mayo stage, and sex significantly associated shorter OS. Specifically, cardiac involvement parameters including ejection fraction <70%, brain natriuretic peptide >400 pg/ml, and interventricular septal thickness >13 mm significantly impacted OS (P = 0.012, 0.0027, < 0.0001, respectively). Multivariate analysis indicated cardiac involvement, lower dose of melphalan, and sex as significant OS factors (P = 0.0223, 0.0168, 0.0335, respectively).

Conclusion

Despite the increasing availability of anti-CD38 antibody-based therapies that may reduce the necessity for HDM/SCT, HDM/SCT remains an effective treatment for patients with AL amyloidosis who have sufficient cardiac function and are deemed suitable for receiving 200 mg/m² of melphalan.