Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2023 S526 lymphocytes, T-cells carrying T-cell receptors, and T-cells carrying chimeric antigen receptors. During treatment with CAR-T cells, the patient’s T lymphocytes were harvested, modified in vitro, and reinfused into the patient to provide greater efficiency and potency in targeting tumor cells. CAR-T immunotherapy has shown remarkable results and has become a promising therapy for treating refractory or relapsed solid cancers. However, several hurdles, such as T cell exhaustion, antigen escape, toxicity, CAR-T cell trafficking, immunosuppressive microenvironment cytokine release syndrome, insertional oncogenesis, and so on, have been associated with CAR-T cells. We are currently conducting clinical trials investigating the use of CRISPR gene therapy. Brazil has ample intellectual and technological capacity to participate in these historical advances and advance CRISPR in cancer therapy. In this work, we will present the ongoing efforts in Brazil regarding the application of CRISPR technology in engineering CAR-T cells and its clinical efficacy and safety in cancer treatment. Keywords: CAR-T, CRISPR/Cas9, Brazil, gene editing, universal CAR-T cells CT-321 Safety and Efficacy of an Academic Anti‑CD19 Chimeric Antigen Receptor (CAR) T‑Cell Therapy for Non‑Hodgkin Lymphoma and Acute Lymphoblastic Leukemia Developed in Brazil: Increasing Access in a Public Health System Bruno Garcia Pires MD1, Diego Villa Clé MD, PhD1,2, Camila Dermínio Donadel MD2, Flávia Mesquita Gava MD1, Leonardo Carvalho Palma MD, PhD1, Gil Cunha De Santis MD, PhD1,2,3, Vanderson Rocha MD, PhD4, Rodrigo do Tocantins Calado MD, PhD1,2, Dimas Tadeu Covas MD, PhD1,2,3 1Department of Medical Imaging, Hematology, and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. 2Regional Blood Center of Ribeirão Preto, Ribeirão Preto Medical School, Ribeirão Preto, Brazil. 3Butantan Institute, São Paulo, Brazil. 4Service of Hematology, Transfusion and Cell Therapy, LIM31, University of Sao Paulo Medical School, São Paulo, Brazil Context: The approval of commercial CAR-T cell products has revolutionized cancer treatment, however, its high cost imposes limiting access to this therapy, especially in low and middle-income countries (LMIC). Thus it is urgent to implement strategies that provide equitable access to this treatment. Objectives: Evaluate the safety and efficacy of administering a locally produced academic anti-CD19 CAR-T cell, in patients diagnosed with relapsed/ refractory B-cell non-Hodgkin lymphoma (NHN) or B-cell acute lymphoblastic leukemia (B-ALL). Design: We developed a secondgeneration anti-CD19 CAR which signals through a 4-1BB and CD3-z endodomain. This is a retrospective observational study in which we evaluated the safety and efficacy data of 13 patients (6 NHL, 7 B-ALL) treated at two centers affiliated with the University of São Paulo, Brazil, between September 2019 and May 2023. Outcomes: We evaluated the toxicity profile associated with the therapy, the overall response rates at day 30 and 90, and overall and relapse-free survival. Results: On day 30, 11 out of 13 (84%) treated patients had disease response (9 complete and 2 partial remissions). One patient died on day 16 due to disease complications, while another patient died on day 19 due to sepsis. On day 90, all patients who had achieved complete remission remained in remission, while one with a partial response experienced disease progression, and the other one died due to a domestic accident. Median follow-up was 232 days. Twelve patients (92%) experienced cytokine release syndrome, the majority grade 1-2, but four (30%) grade 3. Two patients (15%) developed immune effector cell-associated neurotoxicity syndrome, one grade 2 and one grade 4. Early cytopenias were observed in all patients. Other adverse events observed were: disseminated intravascular coagulation (4 patients), hemophagocytic lymphohistiocytosis (2 patients), cytomegalovirus reactivation (3 patients), late cytopenias (3 patients), and hypogammaglobulinemia (9 patients). Conclusion: This study demonstrates the feasibility of an academic CAR-T cell produced in Brazil. While further follow-up is necessary, our findings indicate that locally manufactured products exhibit a favorable response rate and safety profile, and is a promising option to ensure equitable access to healthcare for patients in LMIC. Keywords: Cellular therapy, CAR-T cell, accessibility, public health system CT-342 Prolonged Hematologic Toxicity After B‑Cell Maturation Antigen (BCMA) Chimeric Antigen Receptor (CAR) T‑Cell Treatment: From Clinical Data to Ex‑Vivo Studies at a Single Center Maria Luisa Palacios-Berraquero MD1,2, Nerea Berrastegui PhD student1, Paula Rodríguez-Márquez PhD1, Maria Erendira Calleja Cervantes PhD1,3, Aintzane Zabaleta PhD4, Leire Burgos PhD4, Diego Alignani PhD4, Patxi San Martin-Uriz PhD1, Amaia Vilas-Zornoza PhD1,5, Lorea Jordana MS1, Cristina Calviño MS1, Angel Martín-Mallo PhD1, Saray Rodríguez-Díaz MS1, Susana Inogés MD, PhD6,5, Ascensión Lopez-Díaz de Cerio MD, PhD6,5, Sofia Huerga MD7, Jose Rifón MD, PhD7,5,8, Ana Alfonso MD, PhD7,5,8, Juan José Lasarte PhD9, Mikel Hernaez PhD3, Jesús San Miguel MD, PhD7,1,8,5, Paula Rodriguez-Otero MD, PhD7,5,8, Bruno Paiva PhD1,4,5, Teresa Ezponda PhD1,5, Juan Roberto Rodriguez-Madoz PhD1,5, Felipe Prósper MD, PhD7,1,8,5,10 1Hemato-Oncology Program. Cima Universidad de Navarra. IdiSNA2Hemato-Oncology Program. Cima Universidad de Navarra. IdiSNA, Pamplona, Spain. 2Hospital Ramón y Cajal. Hematology Department., Madrid, Spain. 3Computational Biology Program. Cima Universidad de Navarra, Pamplona, Spain. 4Flow Cytometry Core. Cima Universidad de Navarra, Pamplona, Spain. 5Centro de Investigacion Biomedica en Red de Cancer (CIBERONC)., Madrid, Spain. 6Immunology and Immunotherapy Department. Clinica Universidad de Navarra., Pamplona, Spain. 7Hematology and Cell Therapy Department. Clinica Universidad de Navarra, Pamplona, Spain. 8Cancer Center Universidad de Navarra, Pamplona, Spain.
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