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Safety and efficacy of a new academic CD19-directed CAR-T cell for refractory/relapsed non-Hodgkin lymphoma and acute lymphoblastic leukemia in Brazil

Bone Marrow Transplantation (2024)Cite this article

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CD19-positive acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (B-ALL) have a dismal prognosis when first-line therapy fails [1, 2]. Complete responses in relapsed/refractory (R/R) B-ALL to second-line therapy are 30–45%, with a median overall survival (OS) of only 5–8 months, and is even lower after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [2]. The response rate in R/R diffuse large B-cell lymphoma (DLBCL) is approximately 40% to first-line therapy, and only 15–20% achieve sustained response to autologous HSCT (auto-HSCT) [1]. Chimeric antigen receptor (CAR)-T cells anti-CD19 emerged as a potential curative therapy for B-cell malignancies that failed to standard ones, with response rates up to 80% of R/R B-ALL and DLBCL, superior to conventional therapies [3,4,5,6]. However, commercial CAR-T cell products are expensive [7], fostering alternative CAR-T manufacturing [8, 9]. We report the outcomes in 20 R/R B-NHL or B-ALL patients treated with academic CD19-directed CAR-T cell products.

This is a two-center (Hospital das Clínicas de Ribeirão Preto and Hospital das Clínicas de São Paulo, University of São Paulo) retrospective report on the efficacy and safety of an academic CD19-directed CAR-T cell product (HD37 clone; 4-1BB as costimulatory domain) for patients with R/R B-NHL or B-ALL, treated between 2019 and 2023. Lymphocytes were harvested by apheresis. Afterward, the apheresis products underwent cell selection, activation, transduction, and expansion before cryopreservation. On day zero, CAR-T cell products were thawed and infused after lymphodepletion. We evaluated the incidence and severity of adverse events (AEs), such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, coagulopathy, and hypogammaglobulinemia, and response rate, defined as complete response (CR) or partial response (PR) (B-NHL) or undetected leukemic blasts (B-ALL) on days 30 and 90 after cell infusion. Results were expressed as median (range) and categorical variables as percent. This report was approved by the local Research Ethics Committee (Methods details in Supplementary Material).

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Fig. 1: Overall response in 20 patients (B-ALL: 13; B-NHL: 7) treated with CD19-directed CAR-T cell.

Data availability

The data presented in this report are available on request to the corresponding author.

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Acknowledgements

The authors thank Nathália Cristine André, Sandra Navarro Bresciani, Maristela Delgado Orellana, Lucas Botelho, Amanda Mizukami Martins, Taísa Risque Fernandes, Sâmia Rigotto Caruso, Virginia Picanço-Castro, and Patricia Bonini Vianna for their assistance. We also thank all the personnel involved in CAR-T cell manufacturing.

Funding

Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (process number 2013/08.135-2), São Paulo, Brazil. Butantan Institute, São Paulo, Brazil.

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Authors and Affiliations

  1. Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, Brazil

    Camila D. Donadel, Gil C. De Santis, Thiago E. Gonçalves, Bruno G. Pires, Leonardo C. Palma, Renato Luiz Guerino-Cunha, Dimas T. Covas, Rodrigo T. Calado & Diego V. Clé

  2. Department of Pediatrics, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, Brazil

    Flavia Gava, Joana T. B. Faria, Gabriela V. A. Silva & Luiz Guilherme Darrigo-Junior

  3. Department of Hematology, Hemotherapy & Cell Therapy and Laboratory of Medical Investigation in Pathogenesis and Directed Therapy in Onco-Immuno-Hematology. Hospital das Clínicas da Faculdade de Medicina, University of São Paulo (USP), São Paulo, Brazil

    Giancarlo Fatobene & Vanderson Rocha

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  1. Camila D. Donadel
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Contributions

Conceptualization: Camila D. Donadel, Gil C. De Santis, Renato Luiz Guerino-Cunha, Rodrigo T. Calado, Dimas T. Covas and Diego V. Clé; Methodology: Camila D. Donadel, Gil C. De Santis and Diego V. Clé; Statistical analysis: Thiago Eleutério Gonçalves, Camila D. Donadel and Gil C. De Santis; Data collection: Camila D. Donadel, Bruno G. Pires, Flavia Gava, Giancarlo Fatobene, Joana T. B. Faria, Gabriela V. A. Silva, Luiz Guilherme Darrigo-Junior, Renato Luiz Guerino-Cunha, and Thiago Eleutério Gonçalves; Writing—original draft preparation: Camila D. Donadel, Bruno G. Pires, Gil C. De Santis, Diego V. Clé; Writing—review and editing: Camila D. Donadel, Gil C. De Santis, Giancarlo Fatobene, Flavia Gava, Vanderson Rocha, Rodrigo T. Calado, Diego V. Clé. All authors have read and agreed to the published version of the paper.

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Correspondence to Camila D. Donadel.

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Donadel, C.D., De Santis, G.C., Gonçalves, T.E. et al. Safety and efficacy of a new academic CD19-directed CAR-T cell for refractory/relapsed non-Hodgkin lymphoma and acute lymphoblastic leukemia in Brazil. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02283-6

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