PMID- 37709204 OWN - NLM STAT- MEDLINE DCOM- 20231204 LR - 20231204 IS - 2666-6367 (Electronic) IS - 2666-6367 (Linking) VI - 29 IP - 12 DP - 2023 Dec TI - Long-Term Survivors after Failure of Chimeric Antigen Receptor T Cell Therapy for Large B Cell Lymphoma: A Role for Allogeneic Hematopoietic Cell Transplantation? A German Lymphoma Alliance and German Registry for Stem Cell Transplantation Analysis. PG - 750-756 LID - S2666-6367(23)01547-6 [pii] LID - 10.1016/j.jtct.2023.09.008 [doi] AB - The outcome of patients with large B cell lymphoma (LBCL) who relapse or progress after CD19-directed chimeric antigen receptor T cell therapy (CAR-T) administered as salvage therapy beyond the second treatment line is poor. However, a minority of patients become long-term survivors despite CAR-T failure. The German Lymphoma Alliance (GLA) has proposed a hierarchical management algorithm for CAR-T failure in LBCL, aimed at allogeneic hematopoietic cell transplantation (alloHCT) as definite therapy in eligible patients. The purpose of this study was to investigate characteristics, relapse patterns, and management strategies in long-term survivors after CAR-T failure, with a particular focus on the feasibility and outcome of alloHCT. This was a retrospective analysis of all evaluable patients with a relapse/progression event (REL) observed in a previously reported GLA sample between November 2018 and May 2021. REL occurred in 214 of 356 patients (60%) who underwent CAR-T for LBCL in the previous GLA study. An evaluable dataset was available for 143 of these 214 patients (67%). Twenty-six of 143 patients (18%) survived 12 months or longer from REL, 109 (76%) died within the first year after REL, and 8 (6%) were alive but had not reached the 12-month landmark. Long-term survivors had more favorable pre-CAR-T features, had a longer interval between CAR-T and REL, and had more often received a tumor biopsy after CAR-T failure, whereas the choice of the first salvage regimen had no impact. AlloHCT was feasible in 40 of 53 patients (75%) intended and resulted in a 12-month post-transplantation overall survival of 36% in those patients who underwent transplantation with sensitive or untreated REL. AlloHCT after CAR-T failure in LBCL is feasible and may be an important contributor to long-term survival, although selection bias must be taken into account. Thus, alloHCT should be considered as a reasonable treatment option for eligible patients in this setting. However, because the overall outlook after CAR-T failure remains poor, novel effective therapeutic approaches are needed, either to allow long-term disease control per se or to improve the preconditions for successful alloHCT. CI - Copyright (c) 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved. FAU - Derigs, Patrick AU - Derigs P AD - Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: Patrick.Derigs@med.uni-heidelberg.de. FAU - Bethge, Wolfgang A AU - Bethge WA AD - Department of Internal Medicine II, University Hospital Tuebingen, Tuebingen, Germany. FAU - Kramer, Isabelle AU - Kramer I AD - Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany. FAU - Holtick, Udo AU - Holtick U AD - Department I of Internal Medicine, Medical Faculty and University Hospital of Cologne, University of Cologne, Cologne, Germany. FAU - von Tresckow, Bastian AU - von Tresckow B AD - Department of Hematology and Stem Cell Transplantation, West German Cancer Center and German Cancer Consortium (DKTK partner site Essen), University Hospital Essen, University of Duisburg-Essen, Essen, Germany. FAU - Ayuk, Francis AU - Ayuk F AD - Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Penack, Olaf AU - Penack O AD - Department of Hematology, Oncology and Tumorimmunology, University Hospital Charite Berlin, Berlin, Germany. FAU - Vucinic, Vladan AU - Vucinic V AD - Medical Department for Hematology, Cell Therapy and Hemostaseology, University Hospital Leipzig, Leipzig, Germany. FAU - von Bonin, Malte AU - von Bonin M AD - Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany. FAU - Baldus, Claudia AU - Baldus C AD - Department of Internal Medicine II, University Hospital Schleswig-Holstein, Kiel, Germany. FAU - Mougiakakos, Dimitrios AU - Mougiakakos D AD - Department of Internal Medicine V, University Hospital Erlangen, Erlangen, Germany. FAU - Wulf, Gerald AU - Wulf G AD - Department of Hematology and Medical Oncology, University Medicine Goettingen, Goettingen, Germany. FAU - Schnetzke, Ulf AU - Schnetzke U AD - Department of Internal Medicine II, University Hospital Jena, Jena, Germany. FAU - Stelljes, Matthias AU - Stelljes M AD - Department of Medicine A, University Hospital Muenster, Muenster, Germany. FAU - Fante, Matthias AU - Fante M AD - Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany. FAU - Schroers, Roland AU - Schroers R AD - Department of Hematology and Oncology, Ruhr-University Bochum, Bochum, Germany. FAU - Kroeger, Nicolaus AU - Kroeger N AD - Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Dreger, Peter AU - Dreger P AD - Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany. CN - German Lymphoma Alliance and the German Registry for Stem Cell Transplantation LA - eng PT - Journal Article DEP - 20230913 PL - United States TA - Transplant Cell Ther JT - Transplantation and cellular therapy JID - 101774629 RN - 0 (Receptors, Chimeric Antigen) SB - IM MH - Humans MH - *Receptors, Chimeric Antigen MH - Retrospective Studies MH - Neoplasm Recurrence, Local/etiology MH - *Hematopoietic Stem Cell Transplantation/adverse effects/methods MH - *Lymphoma, Large B-Cell, Diffuse/therapy MH - Registries MH - Recurrence MH - Survivors OTO - NOTNLM OT - Allogeneic hematopoietic cell transplantation OT - CAR-T OT - Lymphoma OT - Relapse EDAT- 2023/09/15 00:42 MHDA- 2023/12/04 12:42 CRDT- 2023/09/14 19:18 PHST- 2023/06/20 00:00 [received] PHST- 2023/08/17 00:00 [revised] PHST- 2023/09/11 00:00 [accepted] PHST- 2023/12/04 12:42 [medline] PHST- 2023/09/15 00:42 [pubmed] PHST- 2023/09/14 19:18 [entrez] AID - S2666-6367(23)01547-6 [pii] AID - 10.1016/j.jtct.2023.09.008 [doi] PST - ppublish SO - Transplant Cell Ther. 2023 Dec;29(12):750-756. doi: 10.1016/j.jtct.2023.09.008. Epub 2023 Sep 13.