1. Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study.
- Author
-
Derigs P, Schubert ML, Dreger P, Schmitt A, Yousefian S, Haas S, Röthemeier C, Neuber B, Hückelhoven-Krauss A, Brüggemann M, Bernhard H, Kobbe G, Lindemann A, Rummel M, Michels B, Korell F, Ho AD, Müller-Tidow C, and Schmitt M
- Abstract
Third-generation chimeric antigen receptor T cells (CARTs) for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) may improve efficacy compared to second-generation CARTs due to their enhanced CAR design. We performed the first phase 1/2 investigator-initiated trial evaluating escalating doses of third-generation CARTs (HD-CAR-1) targeting CD19 in patients with r/r CLL and B-cell lymphoma. CLL eligibility criteria were failure to two therapy lines including at least one pathway inhibitor and/or allogeneic hematopoietic cell transplantation. Nine heavily pretreated patients received HD-CAR-1 at dose levels ranging from 1 × 10
6 to 200 × 106 CART/m2 . In-house HD-CAR-1 manufacturing was successful for all patients. While neurotoxicity was absent, one case of grade 3 cytokine release syndrome was observed. By day 90, six patients (67%) attained a CR, five of these (83%) with undetectable MRD. With a median follow-up of 27 months, 2-year PFS and OS were 30% and 69%, respectively. HD-CAR-1 products of responders contained significantly more CD4 + T cells compared to non-responders. In non-responders, a strong enrichment of effector memory-like CD8 + T cells with high expression of CD39 and/or CD197 was observed. HD-CAR-1 demonstrated encouraging efficacy and exceptionally low treatment-specific toxicity, presenting new treatment options for patients with r/r CLL. Trial registration: #NCT03676504., (© 2024. The Author(s).)- Published
- 2024
- Full Text
- View/download PDF