Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Blood advances, 2022-11, Vol.6 (21), p.5774-5785

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• •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.