Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy

• Published in: Cancers Vol. 13; no. 17; p. 4279
• Main Authors: Lamure, Sylvain, Van Laethem, François, De Verbizier, Delphine, Lozano, Claire, Gehlkopf, Eve, Tudesq, Jean-Jacques, Serrand, Chris, Benzaoui, Mehdi, Kanouni, Tarik, Quintard, Adeline, De Vos, John, Tchernonog, Emmanuelle, Platon, Laura, Ayrignac, Xavier, Ceballos, Patrice, Sirvent, Anne, François, Mickael, Guedon, Hanane, Quittet, Philippe, Mongellaz, Cedric, Conte, Aurélie, Herbaux, Charles, Bret, Caroline, Taylor, Naomi, Dardalhon, Valérie, Cartron, Guillaume
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 25-08-2021; MDPI
• Subjects: Antigens; Apheresis; B-cell lymphoma; Cancer; CD19 antigen; CD4 antigen; CD8 antigen; Cell therapy; Chemotherapy; Cytokines; Disease prevention; Effector cells; Flow cytometry; Genotype & phenotype; Hematology; Human health and pathology; Immunology; Life Sciences; Lymphocytes B; Lymphocytes T; Lymphoma; Memory cells; Metabolic response; Metabolism; Patients; Phenotypes; Software; Statistical analysis; Variables; United States > US; Immune-monitoring; T-cell exhaustion; CAR T-cell; Tisagenleucleucel; Axicabtagene ciloleucel; Standard-of-care; Diffuse large B-cell lymphoma
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13174279

CD19-directed CAR T-cells have been remarkably successful in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and transformed follicular lymphoma (t-FL). In this cohort study, we treated 60 patients with axicabtagene ciloleucel or tisagenlecleucel. Complete and partial metabolic responses (CMR/PMR) were obtained in 40% and 23% of patients, respectively. After 6.9 months of median follow-up, median progression-free survival (mPFS) and overall survival (mOS) were estimated at 3.1 and 12.3 months, respectively. Statistical analyses revealed that CMR, PFS, and OS were all significantly associated with age-adjusted international prognostic index (aaIPI, p < 0.05). T-cell subset phenotypes in the apheresis product tended to correlate with PFS. Within the final product, increased percentages of both CD4 and CD8 CAR+ effector memory cells (p = 0.02 and 0.01) were significantly associated with CMR. Furthermore, higher CMR/PMR rates were observed in patients with a higher maximal in vivo expansion of CAR T-cells (p = 0.05) and lower expression of the LAG3 and Tim3 markers of exhaustion phenotype (p = 0.01 and p = 0.04). Thus, we find that aaIPI at the time of infusion, phenotype of the CAR T product, in vivo CAR T-cell expansion, and low levels of LAG3/Tim3 are associated with the efficacy of CAR T-cell therapy in DLBCL patients.