Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia

• Published in: Blood advances Vol. 6; no. 21; pp. 5774 - 5785
• Main Authors: Gill, Saar, Vides, Vanessa, Frey, Noelle V., Hexner, Elizabeth O., Metzger, Susan, O'Brien, Megan, Hwang, Wei-Ting, Brogdon, Jennifer L., Davis, Megan M., Fraietta, Joseph A., Gaymon, Avery L., Gladney, Whitney L., Lacey, Simon F., Lamontagne, Anne, Mato, Anthony R., Maus, Marcela V., Melenhorst, J. Joseph, Pequignot, Edward, Ruella, Marco, Shestov, Maksim, Byrd, John C., Schuster, Stephen J., Siegel, Donald L., Levine, Bruce L., June, Carl H., Porter, David L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.11.2022; The American Society of Hematology
• Subjects: Antigens, CD19; Disease-Free Survival; Humans; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Neoplasm, Residual - drug therapy; Prospective Studies; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Regular; T-Lymphocytes
• ISSN: 2473-9529; 2473-9537; 2473-9537
• DOI: 10.1182/bloodadvances.2022007317

•Autologous CART-19 can be safely added to ibrutinib.•Addition of CART-19 to ibrutinib leads to frequent, durable, and deep remissions in CLL. [Display omitted] In chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in patients with CLL not in CR despite ≥6 months of ibrutinib. The primary endpoints were safety, feasibility, and achievement of a CR within 3 months. Of 20 enrolled patients, 19 received huCART-19. The median follow-up for all infused patients was 41 months (range, 0.25-58 months). Eighteen patients developed cytokine release syndrome (CRS; grade 1-2 in 15 of 18 subjects), and 5 developed neurotoxicity (grade 1-2 in 4 patients, grade 4 in 1 patient). While the 3-month CR rate among International Working Group on CLL (iwCLL)-evaluable patients was 44% (90% confidence interval [CI], 23-67%), at 12 months, 72% of patients tested had no measurable residual disease (MRD). The estimated overall and progression-free survival at 48 months were 84% and 70%, respectively. Of 15 patients with undetectable MRD at 3 or 6 months, 13 remain in ongoing CR at the last follow-up. In patients with CLL not achieving a CR despite ≥6 months of ibrutinib, adding huCART-19 mediated a high rate of deep and durable remissions. ClinicalTrials.gov number, NCT02640209.