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Immunotherapy

Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/ refractory B cell non-Hodgkin lymphoma

Leukemia volume 33, pages 2540–2544 (2019)Cite this article

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Chimeric antigen receptor (CAR) T cell therapy is a paradigm shift in the management of B cell non-Hodgkin lymphomas (NHL). Two CAR T cell products, axicabtagene ciloleucel (axi-cel, Kite, Gilead) and tisagenlecleucel (Novartis), are now FDA approved based on significant responses in relapsed/ refractory B cell NHL [1, 2]. Neither of these pivotal trials included patients who had undergone a prior allogeneic hematopoietic cell transplantation (alloHCT). We hereby share our experience in four patients who received CAR T cell therapy with axi-cel, following lymphodepletion with fludarabine/cyclophosphamide, for relapsed NHL after alloHCT, where T cells were harvested from recipient following relapse.

A 33-year-old man was diagnosed with T cell rich B cell lymphoma Ann Arbor Stage 4B. He was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) [progression of disease (POD)], rituximab, ifosfamide, carboplatin and etoposide (R-ICE) [complete response (CR)] and then alloHCT from a matched unrelated donor, 14 months after diagnosis [CR]. Post-alloHCT course was complicated by moderate chronic graft versus host disease (GVHD) managed with corticosteroids and tacrolimus. He relapsed 5 years later (off immunosuppression by then) with diffuse lymphadenopathy, and received rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (R-EPOCH) [partial response (PR)], followed by axi-cel. He developed grade 2 cytokine release syndrome (CRS) and grade 2 neurotoxicity (ASBMT consensus grading [3]). PR was noted on day +30, but POD at day +60; and he died day +108 after CAR T cell infusion. There was no reappearance of GVHD following CAR T cells.

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Funding

This research was supported in part by NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Adult Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Tania Jain, Craig S. Sauter, Gunjan L. Shah, Molly A. Maloy, Jason Chan, Michael Scordo, Yakup Batlevi, Parastoo B. Dahi, Sergio A. Giralt & Miguel-Angel Perales

  2. Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, USA

    Craig S. Sauter, Gunjan L. Shah, Michael Scordo, Parastoo B. Dahi, Connie W. Batlevi, M. Lia Palomba, Sergio A. Giralt & Miguel-Angel Perales

  3. Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Scott T. Avecilla

  4. Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Connie W. Batlevi & M. Lia Palomba

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  1. Tania Jain
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Correspondence to Miguel-Angel Perales.

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Conflict of interest

CS—Consultant on advisory boards for: Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Precision Biosciences, Kite, a Gilead Company and GSK. Research funds for investigator-initiated trials from: Juno Therapeutics and Sanofi-Genzyme. GS—Research funding from Janssen and Amgen. MS—Consultancy: Angiocrine Bioscience, Inc., McKinsey & Company. Scott Avecilla—Honoraria for presenting a project in partnership with Abbott Laboratories. CB—Research funding from Epizyme, Novartis, Janssen, BMS, Miragen, Mediimmune; Consultancy from Defined Health, GLG, Guidepoint Global; Honoraria from Dava Oncology. MLP—Advisory Board for Celgene, Consultant for Merck and Pharmacyclics. SG—Advisory Board for Amgen, Actinuum, Celgene, Johnson & Johnson, Jazz pharmaceutical, Takeda, Novartis, Kite, Spectrum Pharma; Research funding from Amgen, Actinuum, Celgene, Johnson & Johnson, Miltenyi, Takeda, Miguel-Angel Perales - Honoraria from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda. He serves on DSMBs for Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. Research support for clinical trials from Incyte, Kite (Gilead) and Miltenyi Biotec.

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Jain, T., Sauter, C.S., Shah, G.L. et al. Safety and feasibility of chimeric antigen receptor T cell therapy after allogeneic hematopoietic cell transplantation in relapsed/ refractory B cell non-Hodgkin lymphoma. Leukemia 33, 2540–2544 (2019). https://doi.org/10.1038/s41375-019-0476-y

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