Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL

• Published in: Blood Vol. 139; no. 26; pp. 3722 - 3731
• Main Authors: Gauthier, Jordan, Gazeau, Nicolas, Hirayama, Alexandre V., Hill, Joshua A., Wu, Vicky, Cearley, Aisling, Perkins, Paula, Kirk, Angela, Shadman, Mazyar, Chow, Victor A., Gopal, Ajay K., Dwinal, Alexandria Hodges, Williamson, Staci, Myers, Jessie, Chen, Andy, Nagle, Sarah, Hayes-Lattin, Brandon, Schachter, Levanto, Maloney, David G., Turtle, Cameron J., Sorror, Mohamed L., Maziarz, Richard T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.06.2022; American Society of Hematology
• Subjects: Antigens, CD19; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive; Lymphoid Neoplasia; Lymphoma, B-Cell - therapy; Receptors, Chimeric Antigen; Retrospective Studies; T-Lymphocytes
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood.2021014497

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase I/II clinical trial (NCT01865617). After adjustment for age, HCT-CI, LDH, largest lesion diameter, and ALC, CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower CRS severity compared to axicel (adjusted OR [aOR], 0.19; 95%CI, 0.08-0.46), with a trend towards lower CRS severity with tisacel compared to axicel (aOR, 0.47; 95%CI, 0.21-1.06; p=0.07). Tisacel (aOR, 0.17; 95%CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95%CI, 0.06-0.47) were both associated with lower ICANS severity compared to axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared to axicel. Although sensitivity analyses using either PET or CT-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel versus axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.