Third-generation anti-CD19 CAR T cells for relapsed/refractory chronic lymphocytic leukemia: a phase 1/2 study

被引：11

作者：

Derigs, Patrick ^{[1
]}

Schubert, Maria-Luisa ^{[1
]}

Dreger, Peter ^{[1
]}

Schmitt, Anita ^{[1
]}

Yousefian, Schayan ^{[2
,3
,4
]}

Haas, Simon ^{[2
,3
,4
,5
,6
,7
]}

Roethemeier, Caroline ^{[2
,3
,4
]}

Neuber, Brigitte ^{[1
]}

Hueckelhoven-Krauss, Angela ^{[1
]}

Brueggemann, Monika ^{[8
]}

Bernhard, Helga ^{[9
]}

Kobbe, Guido ^{[10
]}

Lindemann, Albrecht ^{[11
]}

Rummel, Mathias ^{[12
]}

Michels, Birgit ^{[1
]}

Korell, Felix ^{[1
]}

Ho, Anthony D. ^{[1
,5
]}

Mueller-Tidow, Carsten ^{[1
,5
]}

Schmitt, Michael ^{[1
,5
]}

机构：

[1] Heidelberg Univ Hosp, Internal Med 5 Hematol Oncol & Rheumatol, Heidelberg, Germany

[2] Charite Univ Med Berlin, Berlin Inst Hlth BIH, Berlin, Germany

[3] Berlin Inst Med Syst Biol, Max Delbruck Ctr Mol Med Helmholtz Assoc, Berlin, Germany

[4] Charite Univ Med Berlin, Dept Hematol Oncol & Tumor Immunol, Berlin, Germany

[5] Natl Ctr Tumor Dis NCT, German Canc Res Ctr DKFZ, Heidelberg, Germany

[6] Heidelberg Inst Stem Cell Technol & Expt Med Histe, Heidelberg, Germany

[7] Queen Mary Univ London, Precis Healthcare Univ Res Inst, London, England

[8] Univ Hosp Schleswig Holstein, Dept Internal Med 2, Kiel, Germany

[9] Klinikum Darmstadt, Dept Internal Med 5, Darmstadt, Germany

[10] Univ Hosp Dusseldorf, Dept Hematol Oncol & Clin Immunol, Dusseldorf, Germany

[11] Onkol Ettlingen, Ettlingen, Germany

[12] Univ Hosp Giessen, Dept Internal Med 4, Giessen, Germany

来源：

LEUKEMIA | 2024年 / 38卷 / 11期

关键词：

LISOCABTAGENE MARALEUCEL; LYMPHOMA; CLL; MULTICENTER; REMISSIONS; RESISTANCE; SAFETY; BLOOD; CD28;

D O I：

10.1038/s41375-024-02392-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 x 106 to 200 x 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.

引用

页码：2419 / 2428

页数：10

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