1.
Bortezomib-Based Induction Is Associated with Superior Outcomes in Light Chain Amyloidosis Patients Treated with Autologous Hematopoietic Cell Transplantation Regardless of Plasma Cell Burden
Cornell, R. F., Fraser, R., Costa, L., Goodman, S., Estrada-Merly, N., Lee, C., Hildebrandt, G., Gergis, U., Farhadfar, N., Freytes, C. O., et al
Transplantation and cellular therapy. 2021;27(3):264.e1-264.e7
-
-
-
Free full text
Abstract
The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P < .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P < .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P < .01) and PFS (HR, .43; 95% CI, .26 to .72; P < .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.
Clinical Commentary
What is known?
NIHMS1664451
What did this paper set out to examine?
What did they show?
What are the implications for practice and for future work?
2.
Retrospective analysis of autologous stem cell transplantation for AL amyloidosis: A Study from the Multiple Myeloma Working Group of the Japan Society for Hematopoietic Cell Transplantation
Fuchida, S. I., Kawamura, K., Sunami, K., Tsukada, N., Fujii, S., Ohkawara, H., Usuki, K., Wake, A., Endo, S., Ishiyama, K., et al
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND Autologous stem-cell transplantation (ASCT) is the standard of care for eligible patients with light-chain (AL) amyloidosis, but little is known about it in Asian populations. OBJECTIVE AND STUDY DESIGN To investigate the outcome of and prognostic factors for ASCT, we retrospectively analyzed ASCT cases registered to the Transplant Registry Unified Management Program between December 1999 and December 2015 and extra clinical information collected through a secondary survey. The primary endpoint was overall survival (OS). Hematological response, organ response, and transplant-related mortality were analyzed as secondary endpoints. RESULTS The database search found 330 patients (median age, 57 years; range, 31-74), and the secondary survey provided details of 110 cases (33.3%) finally included. Less than three organs were involved in 56.4%, with cardiac involvement in 57.3%. Performance status (PS) was 0-1 in 83.6%. Conditioning melphalan (MEL) dose was reduced in 54.6%. Overall hematological response was partial response or better in 77.6% and complete response in 49.3%. The 5-year OS was 70.1%. A PS of 0-1 was a factor for a significantly better prognosis in terms of OS. Although survival after ASCT for AL amyloidosis improved over time, poor PS and cardiac involvement had a negative impact on prognosis. The early mortality after ASCT was 6.4%. Poor PS and cardiac involvement led to high early mortalities. A brain natriuretic peptide (BNP) level of 400 pg/ml was associated with worse OS. Our study had several limitations of a retrospective analysis using questionnaire. The depth of response and biomarker responses is significantly limited by the degree of missing data. CONCLUSION Careful patient selection is important for a good outcome of ASCT in patients with AL amyloidosis. Poor PS and cardiac involvement had a negative impact on prognosis and the BNP level was a useful prognostic factor for AL amyloidosis patients who received ASCT.
3.
New Light Chain Amyloid Response Criteria Help Risk Stratification of Patients by Day 100 after Autologous Hematopoietic Cell Transplantation
D'Souza, A., Huang, J., Hari, P.
Biology of Blood & Marrow Transplantation. 2016;22(4):768-70
Abstract
Hematologic response criteria in light chain (AL) amyloidosis were updated in 2012 to incorporate free light chain responses. These criteria have been validated in autologous hematopoietic cell transplantation in AL at 6 and 12 months after transplantation. Using a transplantation registry, we assessed day 100 responses in AL amyloidosis. We validate the prognostic significance of the new criteria at this time point. Further, we show that patients who do not achieve at least a very good partial response by this time point have equally worse outcomes, regardless of depth of response (partial versus no response). Thus, we conclude that the new criteria help identify the poor responders by day 100 after transplantation and that this subset of patients should be studied for early evaluation in consolidation trials. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
4.
Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation in Sweden, long-term results from all patients treated in 1994-2009
Rosengren, S., Mellqvist, U. H., Nahi, H., Forsberg, K., Lenhoff, S., Stromberg, O., Ahlberg, L., Linder, O., Carlson, K.
Bone Marrow Transplantation. 2016;51(12):1569-1572
Abstract
High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated mainly because of the high treatment-related mortality (24% in a randomised study comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long-term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden between 1994 and 2009. Seventy-two patients were treated at eight Swedish centres. Median follow-up was 67.5 months. At least partial response (organ or haematological) was seen in 64% of the patients. Median overall survival was 98 months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In patients with cardiac involvement or multiple organ involvement, survival was significantly shorter, median overall survival 49 and 56 months, respectively. All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in the patients with cardiac involvement. For patients treated in the earlier time period (1994-2001), 100-day mortality was 23.8% compared with 7.8% in the later period (2002-2009). In conclusion, long survival times can be achieved in patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres. Early mortality is high, but with a decreasing trend over time.