Related Experiment Video
Updated: Jun 15, 2025
12:16
A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
14.7K
Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study
Patrick Derigs1, Maria-Luisa Schubert2, Peter Dreger2
1Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany. Patrick.Derigs@med.uni-heidelberg.de.
Leukemia
|August 27, 2024
Summary
Third-generation CAR T-cells (CARTs) show promising efficacy and low toxicity in relapsed/refractory chronic lymphocytic leukemia (CLL). This study highlights HD-CAR-1 as a potential new treatment option for these patients.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) presents a significant unmet need.
- Third-generation chimeric antigen receptor T cells (CARTs) offer enhanced CAR design for potentially improved efficacy over second-generation CARTs.
Purpose of the Study:
- To evaluate the safety and efficacy of escalating doses of third-generation CARTs (HD-CAR-1) targeting CD19 in patients with r/r CLL and B-cell lymphoma.
- To assess manufacturing success, toxicity profiles, and clinical outcomes, including response rates and survival, of HD-CAR-1 therapy.
Main Methods:
- A phase 1/2 investigator-initiated trial was conducted with escalating doses of HD-CAR-1 in heavily pretreated patients with r/r CLL and B-cell lymphoma.
- Eligibility criteria for CLL included failure of at least two prior therapy lines, including a pathway inhibitor and/or prior allogeneic hematopoietic cell transplantation.
- Manufacturing success, cytokine release syndrome (CRS), neurotoxicity, overall response rate (ORR), minimal residual disease (MRD) status, progression-free survival (PFS), and overall survival (OS) were assessed.
Main Results:
- In-house HD-CAR-1 manufacturing was successful for all nine patients treated.
- No neurotoxicity was observed; one patient experienced grade 3 cytokine release syndrome.
- By day 90, six patients (67%) achieved a complete remission (CR), with five (83%) having undetectable MRD.
- With a median follow-up of 27 months, 2-year PFS and OS were 30% and 69%, respectively.
- Responders had significantly more CD4+ T cells in their HD-CAR-1 products compared to non-responders.
Conclusions:
- Third-generation CARTs (HD-CAR-1) demonstrate encouraging efficacy and exceptionally low treatment-related toxicity in patients with r/r CLL.
- HD-CAR-1 represents a promising new therapeutic option for patients with relapsed or refractory CLL, warranting further investigation.
- Analysis of T cell subsets in responders versus non-responders provides insights into potential mechanisms of response and resistance.
