Vincristine, Doxorubicin, and Dexamethasone Induction before Autologous Stem Cell Transplantation in Patients with AL Amyloidosis: A Retrospective Comparison with Frontline Stem Cell Transplantation

Abstract

Objective High-dose melphalan and autologous stem cell transplantation (ASCT) therapy for AL amyloidosis are now associated with reduced mortality based on the application of strict criteria. However, there is no long-term evidence concerning the performance of induction therapy with newer agents, such as bortezomib or daratumumab. Concerns regarding long-term relapse despite treatment with ASCT exist, and missing the opportunity to perform ASCT might occur if induction proves to not be efficacious and cardiac amyloidosis progression deprives the patients of a chance to receive ASCT. We herein report good amyloid control by vincristine, doxorubicin, and dexamethasone (VAD) induction therapy and argue the importance of induction therapy before ASCT. Methods We compared patients who underwent VAD induction and ASCT (VAD+ASCT) with patients who underwent frontline ASCT in our hospital. Patients A total of 26 patients with histologically proven AL amyloidosis were included (18 in the VAD+ASCT group and 8 in the frontline ASCT). Results In the VAD+ASCT group, the 10-year overall survival and renal response rates were 82% and 43%, respectively. The renal response rate at two years in the VAD+ASCT group was significantly better than that in the frontline ASCT group. Although there was no significant difference in the survival rates between the two groups, the time to next treatment or death was significantly better in the VAD+ASCT group than in the the frontline ASCT group. Acute kidney injury was the most frequent reason for failure to receive two courses of VAD, and early mortality was mainly due to gastrointestinal complications. Conclusion Considering that only those who underwent 2 courses of VAD experienced a 10-year renal response, induction therapy was deemed to be directly related to the long-term control of AL amyloidosis.

Keywords: AL amyloidosis; VAD induction chemotherapy; autologous hematopoietic stem cell transplantation; nephrotic syndrome.

Figure.

Kaplan-Meier curve for the overall survival of the VAD+ASCT and frontline ASCT groups (A). The frontline ASCT group had a shorter observation period than the VAD+ASCT group; thus, all patients had censored data. Numbers at risk are indicated below the graph. The p value of the log-rank test is indicated. Kaplan-Meier curve for the TNTD of the VAD+ASCT and frontline ASCT groups (B). Numbers at risk are indicated below the graph. The p value of the log-rank test is indicated. VAD: vincristine, adriamycin, dexamethasone autologous stem cell transplantation, ASCT: autologous stem cell transplantation, TNTD: time to next treatment or death