1.
Risk factors, treatments and outcomes of patients with light chain amyloidosis who relapse after autologous stem cell transplantation
Zhang, Y., Guo, J., Chen, W., Zhao, L., Huang, X.
Bone marrow transplantation. 2023
Abstract
Relapse after ASCT is an important factor affecting the long-term prognosis of patients with AL amyloidosis. However, the risk factors of relapse are unknown and there are limited studies on treatment outcomes of these patients. We retrospectively reviewed 170 patients with AL amyloidosis who underwent ASCT between 2010 and 2021. Seventy-six patients confirmed as relapse and the median time from ASCT to relapse was 39 months. On multivariate analysis of variables before and after ASCT, lambda restricted, dFLC >30 mg/L pre ASCT, reduced dose melphalan and dFLC >10 mg/L at 6 months after ASCT were independent risk factors for relapse, and achieving CR after induction therapy and renal response after ASCT were protective factors. Most relapsed patients were treated with bortezomib-based regimens (50%) followed by daratumumab-based regimens (22.2%) and other chemotherapy regimens (13.9%). The overall hematological response in evaluable patients was 68.2% with 56.8% achieving CR/VGPR. The median PFS and OS from post-transplant relapse were 25 months and 81 months, respectively. Patients receiving bortezomib or daratumumab showed a better survival compared to other chemotherapy regimens. In conclusion, this study identified independent risk factors of post-transplant relapse and demonstrated the superiority of bortezomib or daratumumab treatment for these patients. CLINICAL TRIAL REGISTRATION NCT04210791.
2.
The role of induction therapy before autologous stem cell transplantation in low disease burden AL amyloidosis patients
Huang, X., Ren, G., Chen, W., Guo, J., Zhao, L., Zeng, C., Ge, Y., Liu, Z.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2020;:1-9
Abstract
BACKGROUND Induction therapy is recommended before autologous stem cell transplantation (ASCT) for AL amyloidosis patients with high disease burden [bone marrow plasma cells (BMPCs) > 10%], but the role of induction therapy before ASCT in patients with low disease burden (BMPCs ≤ 10%) is still unknown. METHODS A total of 227 patients with AL amyloidosis were included in this study. Among 227 patients, 124 patients received bortezomib-based induction prior to ASCT and were defined as group A, 35 patients received other chemotherapeutic induction and were defined as group B, and the other 68 patients without induction were defined as group C. We compared the differences of efficacy and prognosis between the three groups. RESULTS The haematological overall response rates (ORR) of groups A, B and C were 91%, 67% and 75%, respectively. The complete response rates (CR) of groups A, B and C were 50%, 25% and 20%, respectively. Both the ORR and CR rates of group A were significantly higher than those of groups B and C. The renal response rates of groups A, B and C were 64%, 46% and 47%, respectively. The cardiac response rates of groups A, B and C were 74%, 45% and 40%, respectively. The renal and cardiac responses rates of group A were also significantly higher than those of the other two groups. After a median follow-up of 44 months, the median OS was not reached. The 5-year estimated overall survival (OS) rates of groups A, B and C were 81%, 57% and 67%, respectively. The median progression-free survival (PFS) was 83 months for all patients. The 5-year estimated PFS rates of groups A, B and C were 61%, 38% and 49%, respectively. Both the OS and PFS of group A were higher than those of both group B and group C. On multivariate analysis, baseline dFLC > 50 mg/L was associated with worse survival, but induction with bortezomib was associated with better survival. CONCLUSION Our study demonstrated that low disease burden AL patients who are eligible for ASCT may benefit from bortezomib-based induction therapy.
3.
Combination of bortezomib in the induction, conditioning and consolidation with autologous hematopoietic stem cell transplantation in patients with immunoglobulin light chain amyloidosis
Huang, X., Fu, Z., Chen, L., Chen, W., Ren, G., Guo, J., Zhao, L., Zeng, C., Zhang, H., Gong, D., et al
American journal of hematology. 2019
Abstract
Bortezomib and autologous hematopoietic stem cell transplantation (ASCT) are both active regimen in AL amyloidosis. In this study, we assessed safety and efficacy of combination of bortezomib in the induction, conditioning and consolidation with ASCT in patients with newly diagnosed AL amyloidosis. Treatment schedule consisted of two cycles of bortezomib and dexamethasone (BD) induction therapy, ASCT treatment (the conditioning regimen consisted of melphalan and bortezomib), and four additional 21-day cycles of bortezomib treatment after ASCT. Twenty-one patients were enrolled in the study. Nine patients had cardiac involvement. The overall response rate (ORR) was 90% (18/20) at 12 months after ASCT in evaluable patients, including 10 patients (50%) with complete response, 7 patients (35%) with very good partial response. The organ response rate was 72.2%. The renal and cardiac response was 55% and 40% at 12 months after ASCT respectively, and reached to 66.7% and 50% at 24 months. Peripheral neuropathy and infection were the common adverse events during the treatment, and five patients have been discontinued bortezomib for neuropathy. No death occurred in this study. After a median follow-up of 53 months, the overall survival was 100%, and the estimated progression free survival was 79.9% at 60 months. Data from this study demonstrate that incorporating bortezomib into induction, conditioning and consolidation with ASCT yielded a high rate of hematologic response with tolerable toxicity in patients with AL amyloidosis. The overall survival and progression-free survival also improved after long term follow-up in these patients. (ClinicalTrial.gov Identifier: NCT01273844). This article is protected by copyright. All rights reserved.