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

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 23; p. S526
• Main Authors: Pires, Bruno Garcia, Clé, Diego Villa, Donadel, Camila Dermínio, Gava, Flávia Mesquita, Palma, Leonardo Carvalho, De Santis, Gil Cunha, Rocha, Vanderson, Calado, Rodrigo do Tocantins, Covas, Dimas Tadeu
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2023
• Subjects: accessibility; CAR-T cell; Cellular therapy; public health system; accessibility; CAR-T cell; public health system; Cellular therapy
• DOI: 10.1016/S2152-2650(23)01507-0
• ISSN: 2152-2650

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. 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). We developed a second-generation 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. We evaluated the toxicity profile associated with the therapy, the overall response rates at day 30 and 90, and overall and relapse-free survival. 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). 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.