Bortezomib and autoimmune hemolytic anemia: a systematic review and meta-analysis
DOI:
https://doi.org/10.54097/j43d1z38Keywords:
Bortezomib; Autoimmune Hemolytic Anemia; Relapsed and Refractory; Systematic Review; Meta-Analysis; Salvage Therapy.Abstract
Conventional treatments for autoimmune hemolytic anemia (AIHA) are associated with drawbacks including high recurrence rates and limited therapeutic efficacy. As a proteasome inhibitor, bortezomib demonstrates potential value in relapsed/refractory AIHA, yet existing evidence mostly consists of small-sample case reports without quantitative integrated analyses. The results of this meta-analysis revealed that the pooled overall response rate (ORR) of bortezomib for AIHA was 81% (95%CI: 0.71–0.92), with extremely low inter-study heterogeneity (I²=0.0%, P=0.950). After excluding 2 conference abstracts, the pooled ORR of the remaining 4 full-text studies reached 82% (95%CI: 0.69–0.94), and leave-one-out sensitivity analysis identified no single study exerting a significant impact on the overall conclusions. Current evidence indicates that bortezomib can serve as a second-line salvage therapy for relapsed/refractory patients. However, the included studies were predominantly single-arm retrospective small-sample trials, lacking long-term safety data, failing to differentiate therapeutic effects between warm-type AIHA and cold agglutinin disease subgroups, and containing no controlled trials for direct comparisons with conventional regimens. In conclusion, bortezomib delivers stable efficacy and acceptable tolerability in relapsed/refractory AIHA. Large-sample, multicenter, prospective controlled studies are still required to clarify the optimal administration regimen, eligible patient populations and long-term safety profiles.
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References
[1] Hill, Q.A., et al., The diagnosis and management of primary autoimmune haemolytic anaemia. Br J Haematol, 2017. 176(3): p. 395-411.
[2] Chinese guideline for the diagnosis and treatment of adult autoimmune hemolytic anemia (2023)]. Zhonghua Xue Ye Xue Za Zhi, 2023. 44(1): p. 12-18.
[3] Berentsen, S. and W. Barcellini, Autoimmune Hemolytic Anemias. N Engl J Med, 2021. 385(15): p. 1407-1419.
[4] Yue, W.R., T. Wu, and X.Q. Wang, [The treatment strategies of autoimmune hemolytic anemia]. Zhonghua Xue Ye Xue Za Zhi, 2024. 45(6): p. 615-620.
[5] Lin, X., et al., Rituximab Plus Bortezomib for Relapsed and Refractory Warm Autoimmune Hemolytic Anemia: A Prospective Phase 2 Trial. Am J Hematol, 2025. 100(2): p. 326-329.
[6] Pasquale, R., et al., Bortezomib in autoimmune hemolytic anemia and beyond. Ther Adv Hematol, 2021. 12: p. 20406207211046428.
[7] Johnson, E., et al., Bortezomib for the Management of Relapsed or Refractory Warm Autoimmune Hemolytic Anemia: A Scoping Review. Blood, 2021. 138.
[8] Khandelwal, P., et al., Bortezomib Is a Successful Therapeutic Agent for Refractory Autoimmune Cytopenias in Children: A Single Center Experience. Biology of Blood and Marrow Transplantation, 2014. 20(2): p. S174-S174.
[9] Ratnasingam, S., et al., Bortezomib Yields High Response Rates in Antibody-Mediated Autoimmune Hematological Diseases Refractory to Conventional Immunosuppression. Blood, 2015. 126(23).
[10] 10. Ratnasingam, S., et al., Bortezomib-based antibody depletion for refractory autoimmune hematological diseases. Blood Advances, 2016. 1(1): p. 31-35.
[11] Rossi, G., et al., Short Course of Bortezomib in Anemic Patients with Refractory or Relapsed Cold Agglutinin Disease. a Phase II Prospective Study By the Gimema Group. Blood, 2017. 130.
[12] Zine, M., et al., BORTEZOMIB FOR STEROID-REFRACTORY RITUXIMAB AUTOIMMUNITY AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION. Haematologica, 2017. 102: p. 858-858.
[13] Fadlallah, J., et al., Bortezomib and dexamethasone, an original approach for treating multi-refractory warm autoimmune haemolytic anaemia. British Journal of Haematology, 2019. 187(1): p. 124-128.
[14] Yao, M.K., et al., Combination of low-dose rituximab, bortezomib and dexamethasone for the treatment of autoimmune hemolytic anemia. Medicine, 2022. 101(4).
[15] McGlothlin, J., et al., Bortezomib and daratumumab in refractory autoimmune hemolytic anemia. American Journal of Hematology, 2023. 98(10): p. E263-E265.
[16] Jain, A., et al., Efficacy and Safety of Weekly Bortezomib-dexamethasone as the Third-Line Therapy for Warm Autoimmune Hemolytic Anemia: a Case Series of 5 Patients. Indian Journal of Hematology and Blood Transfusion, 2025. 41(1): p. 144-150.
[17] Chao, S.H., et al., Efficacy and safety of rituximab in autoimmune and microangiopathic hemolytic anemia: a systematic review and meta-analysis. Exp Hematol Oncol, 2020. 9: p. 6.
[18] Reynaud, Q., et al., Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies. Autoimmun Rev, 2015. 14(4): p. 304-13.
[19] Barcellini, W., et al., Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood, 2014. 124(19): p. 2930-6.
[20] Birgens, H., et al., A phase III randomized trial comparing glucocorticoid monotherapy versus glucocorticoid and rituximab in patients with autoimmune haemolytic anaemia. Br J Haematol, 2013. 163(3): p. 393-9.
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