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| Item Type: | Article |
|---|---|
| Title: | Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study |
| Creators Name: | Derigs, P., Schubert, M.L., 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, A.D., 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 × 10(6) CART/m(2). 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. |
| Keywords: | Chronic Lymphocytic Leukaemia, Immunotherapy, Phase I Trials, Phase II Trials, Translational Research |
| Source: | Leukemia |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date: | 27 August 2024 |
| Official Publication: | https://doi.org/10.1038/s41375-024-02392-7 |
| PubMed: | View item in PubMed |
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