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<p>The ASH Annual Meeting 2025 highlighted major advances in allogeneic hematopoietic stem cell transplantation (HSCT), cellular immunotherapy, and graft-versus-host disease (GvHD). A key focus was graft engineering. In the Phase I ORCA-Q trial, selectively engineered allogeneic grafts achieved reliable engraftment without primary graft failure and showed low rates of severe acute and chronic GvHD, infections, and non-relapse mortality. Notably, favorable outcomes were observed even without conventional pharmacological GvHD prophylaxis, supporting graft engineering as a promising strategy to improve immune reconstitution while reducing transplant-related toxicity. Another innovative approach, termed “DLI 2.0,” combines memory T cells with leukemia-specific T-cell receptors (TCRs) to enhance graft-versus-leukemia effects while minimizing GvHD risk. In a Phase I study, TCR-modified memory T cells demonstrated excellent safety, with no GvHD, cytokine release syndrome, or neurotoxicity. Clinical responses were observed in several patients, including a durable remission in high-risk AML. In multiple myeloma, the first clinical data on in vivo CAR-T generation were presented. Using a targeted lentiviral vector, anti-BCMA CAR T cells were generated directly in patients without ex vivo manufacturing or lymphodepletion. All treated patients achieved MRD negativity, with only mild cytokine release syndrome and no neurotoxicity reported. The ROCCA analysis addressed sequencing of CAR-T therapy and HSCT in adult B-ALL. Patients receiving brexucabtagene autoleucel after post-transplant relapse showed superior relapse-free survival, while transplant-naïve patients benefited from consolidative HSCT after CAR-T therapy. In GvHD prevention, the ABA2 trial demonstrated that adding abatacept to standard prophylaxis significantly reduced severe acute GvHD and improved survival outcomes in mismatched unrelated donor transplantation. Finally, elevated thymic stromal lymphopoietin (TSLP) levels emerged as a potential biomarker for severe intestinal GvHD, supporting future evaluation of TSLP-targeted therapies such as tezepelumab. Refined strategies of immunomodulation and immunosuppression are increasingly used to optimize efficacy while improving safety.</p>

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New trends in stem cell transplantation and CAR T-cell therapy—an update from the ASH meeting 2025

  • 期刊论文

  • 发表日期：

    2026年6月23日

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  • Alexandra Donschachner,
  • Julia Cserna

摘要

The ASH Annual Meeting 2025 highlighted major advances in allogeneic hematopoietic stem cell transplantation (HSCT), cellular immunotherapy, and graft-versus-host disease (GvHD). A key focus was graft engineering. In the Phase I ORCA-Q trial, selectively engineered allogeneic grafts achieved reliable engraftment without primary graft failure and showed low rates of severe acute and chronic GvHD, infections, and non-relapse mortality. Notably, favorable outcomes were observed even without conventional pharmacological GvHD prophylaxis, supporting graft engineering as a promising strategy to improve immune reconstitution while reducing transplant-related toxicity. Another innovative approach, termed “DLI 2.0,” combines memory T cells with leukemia-specific T-cell receptors (TCRs) to enhance graft-versus-leukemia effects while minimizing GvHD risk. In a Phase I study, TCR-modified memory T cells demonstrated excellent safety, with no GvHD, cytokine release syndrome, or neurotoxicity. Clinical responses were observed in several patients, including a durable remission in high-risk AML. In multiple myeloma, the first clinical data on in vivo CAR-T generation were presented. Using a targeted lentiviral vector, anti-BCMA CAR T cells were generated directly in patients without ex vivo manufacturing or lymphodepletion. All treated patients achieved MRD negativity, with only mild cytokine release syndrome and no neurotoxicity reported. The ROCCA analysis addressed sequencing of CAR-T therapy and HSCT in adult B-ALL. Patients receiving brexucabtagene autoleucel after post-transplant relapse showed superior relapse-free survival, while transplant-naïve patients benefited from consolidative HSCT after CAR-T therapy. In GvHD prevention, the ABA2 trial demonstrated that adding abatacept to standard prophylaxis significantly reduced severe acute GvHD and improved survival outcomes in mismatched unrelated donor transplantation. Finally, elevated thymic stromal lymphopoietin (TSLP) levels emerged as a potential biomarker for severe intestinal GvHD, supporting future evaluation of TSLP-targeted therapies such as tezepelumab. Refined strategies of immunomodulation and immunosuppression are increasingly used to optimize efficacy while improving safety.