Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib

被引：519

作者：

Turtle, Cameron J. ^{[1
,2
]}

Hay, Kevin A. ^{[1
]}

Hanafi, Laila-Aicha ^{[1
]}

Li, Daniel ^{[3
]}

Cherian, Sindhu ^{[2
]}

Chen, Xueyan ^{[2
]}

Wood, Brent ^{[2
]}

Lozanski, Arletta ^{[4
]}

Byrd, John C. ^{[4
]}

Heimfeld, Shelly ^{[1
]}

Riddell, Stanley R. ^{[1
,2
]}

Maloney, David G. ^{[1
,2
]}

机构：

[1] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA

[2] Univ Washington, Seattle, WA 98195 USA

[3] Juno Therapeut, Seattle, WA USA

[4] Ohio State Univ, Columbus, OH 43210 USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2017年 / 35卷 / 26期

关键词：

B-CELL; LUGANO CLASSIFICATION; SUSTAINED REMISSIONS; RESPONSE CRITERIA; OPEN-LABEL; LYMPHOMA; THERAPY; RESISTANCE; OUTCOMES; TRIAL;

D O I：

10.1200/JCO.2017.72.8519

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose We evaluated the safety and feasibility of anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy in patients with chronic lymphocytic leukemia (CLL) who had previously received ibrutinib. Methods Twenty-four patients with CLL received lymphodepleting chemotherapy and anti-CD19 CAR-T cells at one of three dose levels (2 3 105, 2 3 106, or 2 3 107 CAR-T cells/kg). Nineteen patients experienced disease progression while receiving ibrutinib, three were ibrutinib intolerant, and two did not experience progression while receiving ibrutinib. Six patients were venetoclax refractory, and 23 had a complex karyotype and/or 17p deletion. Results Four weeks after CAR-T cell infusion, the overall response rate (complete response [CR] and/or partial response [PR]) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria was 71% (17 of 24). Twenty patients (83%) developed cytokine release syndrome, and eight (33%) developed neurotoxicity, which was reversible in all but one patient with a fatal outcome. Twenty of 24 patients received cyclophosphamide and fludarabine lymphodepletion and CD19 CAR-T cells at or below the maximum tolerated dose (<= 2 3 10(6) CAR-T cells/kg). In 19 of these patients who were restaged, the overall response rate by IWCLL imaging criteria 4 weeks after infusion was 74% (CR, 4/19, 21%; PR, 10/19, 53%), and 15/17 patients (88%) with marrow disease before CAR-T cells had no disease by flow cytometry after CAR-T cells. Twelve of these patients underwent deep IGH sequencing, and seven (58%) had no malignant IGH sequences detected in marrow. Absence of the malignant IGH clone in marrow of patients with CLL who responded by IWCLL criteria was associated with 100% progression-free survival and overall survival (median 6.6 months follow-up) after CAR-T cell immunotherapy. The progression-free survival was similar in patients with lymph node PR or CR by IWCLL criteria. Conclusion CD19 CAR-T cells are highly effective in high-risk patients with CLL after they experience treatment failure with ibrutinib therapy. (C) 2017 by American Society of Clinical Oncology

引用

页码：3010 / +

页数：15

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