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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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Utilization of Chimeric Antigen Receptor (CAR) T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B cell non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy
Jain, T., Bar, M., Kansagra, A. J., Chong, E. A., Hashmi, S. K., Neelapu, S. S., Byrne, M., Jacoby, E., Lazaryan, A., Jacobson, C. A., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Axicabtagene ciloleucel (YESCARTA(R), Kite Pharma, a Gilead Company) and tisagenlecleucel (KYMRIAH(R), Novartis Pharmaceuticals Corp.) are two CD19-directed chimeric antigen receptor T cell (CD19 CAR T) products that are currently approved by the U.S. Food and Drug Administration, the European Medicines Agency, Health Canada, Ministry of Health, Labor and Welfare (Japan) and Therapeutic Goods Administration (Australia) for treatment of specific subtypes of relapsed/ refractory aggressive B cell non-Hodgkin lymphoma (NHL). While this approval has been transformative in the use of cellular immunotherapy in lymphoma, there are concerns regarding appropriate utilization of this novel therapy, as well as short- and long-term toxicities. To address these issues, representatives of American Society of Transplantation and Cellular Therapy (ASTCT) convened to recognize and address key issues surrounding the clinical application of CD19 CAR T cell therapy in B cell lymphomas, in collaboration with worldwide experts and members of International Society of Cell and Gene Therapy (ISCT), American Society of Hematology (ASH), Foundation for the Accreditation of Cellular Therapy (FACT) and European Society for Blood and Marrow Transplantation (EBMT). The aim of this article is to provide consensus opinion from experts in the fields of hematopoietic cell transplantation, cellular immunotherapy, and lymphoma regarding key clinical questions pertinent to the utilization of CD19 CAR T for the treatment of NHL. As the clinical practice using CAR T cells grows worldwide, we anticipate that this guidance will be relevant for hematology/oncology physicians who care for patients with lymphomas.
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Autologous stem cell transplantation for primary mediastinal B-cell lymphoma: long-term outcome and role of post-transplant radiotherapy. A report of the European Society for Blood and Marrow Transplantation
Avivi, I., Boumendil, A., Finel, H., Nagler, A., de Sousa, A. B., Santasusana, J. M. R., Vandenberghe, E., Afanasyev, B., Bordessoule, D., Moraleda, J. M., et al
Bone marrow transplantation. 2018
Abstract
The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.
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Long-term outcome analysis of reduced-intensity allogeneic stem cell transplantation in patients with mantle cell lymphoma: a retrospective study from the EBMT Lymphoma Working Party
Robinson, S. P., Boumendil, A., Finel, H., Peggs, K. S., Chevallier, P., Sierra, J., Finke, J., Poiré, X., Maillard, N., Milpied, N., et al
Bone marrow transplantation. 2018;53(5):617-624
Abstract
Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved for patients with mantle cell lymphoma who relapse after an autoSCT. However, the long-term efficacy of RIST and its curative potential have not been clearly demonstrated. We studied the long-term outcome of patients receiving a RIST for MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range 31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and 5 years, respectively, and was associated with chemorefractory disease (HR 0.49, p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression-free survival rate and overall survival rate was 31 and 40%, respectively. RIST results in long-term disease-free survival in about 30% of the patients, including those patients relapsing after a prior autoSCT.
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Autologous stem cell transplantation for relapsed/refractory diffuse large B-cell lymphoma: efficacy in the rituximab era and comparison to first allogeneic transplants. A report from the EBMT Lymphoma Working Party
Robinson, S. P., Boumendil, A., Finel, H., Blaise, D., Poire, X., Nicolas-Virelizier, E., Or, R., Malladi, R., Corby, A., Fornecker, L., et al
Bone Marrow Transplantation. 2016;51(3):365-71
Abstract
In the era of chemoimmunotherapy, the optimal treatment paradigm for relapsed and refractory diffuse large B-cell lymphoma has been challenged. We reviewed the outcome of standard salvage therapy with an autologous stem cell transplant (autoSCT) over the last two decades and the outcome of allogeneic SCT (alloSCT) in the most recent decade. AutoSCT recipients diagnosed between 1992 and 2002 (n=2737) were compared with those diagnosed between 2002 and 2010 (n=3980). Patients diagnosed after 2002 had a significantly lower non-relapse mortality (NRM) and relapse incidence (RI) and a superior PFS and overall survival (OS). A total of 4210 patients diagnosed between 2002 and 2010 underwent either an autoSCT or an alloSCT as their first transplant procedure. Two-hundred and thirty patients received an alloSCT (myeloablative (MACalloSCT) n=132, reduced intensity (RICalloSCT) n=98). The 4-year NRM rates were 7%, 20% and 27% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year RI was 45%, 40% and 38% for autoSCT, RICalloSCT and MACalloSCT, respectively (NS). The 4-year PFS were 48%, 52% and 35% for autoSCT, RICalloSCT and MACalloSCT, respectively. The 4-year OS was 60%, 52% and 38% for autoSCT, RIC alloSCT and MACalloSCT, respectively. After adjustment for confounding factors NRM was significantly worse for patients undergoing alloSCT whilst there was no difference in the RI.