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Allogeneic Hematopoietic Cell Transplantation After CAR T-cell Therapy in Large B-cell Lymphoma: Allogeneic-HCT after CAR T-cell therapy
Fried, S., Shouval, R., Walji, M., Flynn, J. R., Yerushalmi, R., Shem-Tov, N., Danylesko, I., Tomas, A. A., Fein, J. A., Devlin, S. M., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has transformed the care of relapsed-refractory large B-cell lymphoma (LBCL). However, approximately 60% of CAR-T recipients will ultimately experience disease recurrence or progression. Salvage therapies after CAR-T treatment failures are of limited efficacy and have a short duration of response. OBJECTIVES To evaluate the role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR T-cell therapy in LBCL patients. STUDY DESIGN A multicenter observational study reporting the outcome of 39 adult LBCL patients receiving allo-HCT following anti CD19-CAR T-cell therapy. RESULTS The median age was 47 years (range 20-68). HLA-matched sibling, HLA-matched unrelated, and alternative donors were utilized in 36%, 36%, and 28% of transplant recipients, respectively. Conditioning regimens were primarily of low or intermediate intensity. Disease status at allo-HCT was CR (41%), PR (38%), or progressive disease (21%). Allo-HCT was performed at a median of 127 days (82-206) after CAR-T therapy. A high incidence of hepatic toxicity (28%), including sinusoidal obstruction syndrome (15.4% [95% CI: 6.2 - 28.5]), was observed. The one-year cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease was 38.5% (95% CI: 23.2-53.6) and 15.4% (95%CI: 6.1-28.5), respectively. The 2-year cumulative incidence of moderate-severe chronic GvHD was 11.1% (95% CI: 3.3-24.3). Overall, 2-year non-relapse mortality and relapse/ progression incidence were 26% (95% CI: 13-41) and 43% (95% CI: 27-59), respectively. With a median follow-up of 32 months, the 2-years overall survival (OS) and progression-free survival (PFS) were 45% (95% CI: 31-66) and 31% (95%CI: 19-50), respectively. In multivariable analyses, pre-HCT elevated LDH and transformed lymphoma were predictive of OS and PFS, respectively. CONCLUSION Allo-HCT after CD19-CAR-T treatment failure is feasible with a relatively promising efficacy but possibly high toxicity rates.
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Management of Adults and Children receiving CAR T-cell therapy: 2021 Best Practice Recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association (EHA)
Hayden, P. J., Roddie, C., Bader, P., Basak, G. W., Bonig, H., Bonini, C., Chabannon, C., Ciceri, F., Corbacioglu, S., Ellard, R., et al
Annals of oncology : official journal of the European Society for Medical Oncology. 2021
Abstract
BACKGROUND Several commercial and academic autologous chimeric antigen receptor T-cell products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, high-grade B-cell lymphoma, and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future. DESIGN EBMT-JACIE and the European Haematology association (EHA) proposed to draft best practice recommendations based on the current literature, to support healthcare professionals in delivering consistent, high-quality care in this rapidly moving field RESULTS Thirty-six CAR-T experts (medical; nursing; pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues. CONCLUSIONS We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for hematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.
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Pre-transplant MRD negativity predicts favorable outcomes of CAR-T therapy followed by haploidentical HSCT for relapsed/refractory acute lymphoblastic leukemia: a multi-center retrospective study
Zhao, H., Wei, J., Wei, G., Luo, Y., Shi, J., Cui, Q., Zhao, M., Liang, A., Zhang, Q., Yang, J., et al
Journal of hematology & oncology. 2020;13(1):42
Abstract
BACKGROUND Consolidative allogeneic hematopoietic stem cell transplantation is a controversial option for patients with relapsed/refractory acute lymphoblastic leukemia after chimeric antigen receptor T cell (CAR-T) therapy. We performed a multicenter retrospective study to assess whether patients can benefit from haploidentical hematopoietic stem cell transplantation after CAR-T therapy. METHODS A total of 122 patients after CAR-T therapy were enrolled, including 67 patients without subsequent transplantation (non-transplant group) and 55 patients with subsequent haploidentical hematopoietic stem cell transplantation (transplant group). Long-term outcome was assessed, as was its association with baseline patient characteristics. RESULTS Compared with the non-transplant group, transplantation recipients had a higher 2-year overall survival (OS; 77.0% versus 36.4%; P < 0.001) and leukemia-free survival (LFS; 65.6% versus 32.8%; P < 0.001). Multivariate analysis showed that minimal residual disease (MRD) positivity at transplantation is an independent factor associated with poor LFS (P = 0.005), OS (P = 0.035), and high cumulative incidence rate of relapse (P = 0.045). Pre-transplant MRD-negative recipients (MRD- group) had a lower cumulative incidence of relapse (17.3%) than those in the non-transplant group (67.2%; P < 0.001) and pre-transplant MRD-positive recipients (MRD+ group) (65.8%; P = 0.006). The cumulative incidence of relapse in MRD+ and non-transplant groups did not differ significantly (P = 0.139). The 2-year LFS in the non-transplant, MRD+, and MRD- groups was 32.8%, 27.6%, and 76.1%, respectively. The MRD- group had a higher LFS than the non-transplantation group (P < 0.001) and MRD+ group (P = 0.007), whereas the LFS in the MRD+ and non-transplant groups did not differ significantly (P = 0.305). The 2-year OS of the MRD- group was higher than that of the non-transplant group (83.3% versus 36.4%; P < 0.001) but did not differ from that of the MRD+ group (83.3% versus 62.7%; P = 0.069). The OS in the non-transplant and MRD+ groups did not differ significantly (P = 0.231). CONCLUSION Haploidentical hematopoietic stem cell transplantation with pre-transplant MRD negativity after CAR-T therapy could greatly improve LFS and OS in patients with relapsed/refractory acute lymphoblastic leukemia. TRIAL REGISTRATION The study was registered in the Chinese clinical trial registry (ChiCTR1900023957).
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Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)-an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)
Kansagra, A. J., Frey, N. V., Bar, M., Laetsch, T. W., Carpenter, P. A., Savani, B. N., Heslop, H. E., Bollard, C. M., Komanduri, K. V., Gastineau, D. A., et al
Bone marrow transplantation. 2019
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Abstract
On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.
PICO Summary
Population
Children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia
Intervention
Expert opinion on clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia
Comparison
None
Outcome
An initial roadmap for navigating common clinical practice scenarios since the approval of the first commercially available CAR-T product for B-ALL.