We previously reported durable responses in relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) patients treated with CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell immunotherapy after ibrutinib failure. Because preclinical studies showed that ibrutinib could improve CAR T cell-antitumor efficacy and reduce cytokine release syndrome (CRS), we conducted a pilot study to evaluate the safety and feasibility of administering ibrutinib concurrently with CD19 CAR T-cell immunotherapy. Nineteen CLL patients were included. The median number of prior therapies was 5, and 17 patients (89%) had high-risk cytogenetics (17p deletion and/or complex karyotype). Ibrutinib was scheduled to begin ≥2 weeks before leukapheresis and continue for ≥3 months after CAR T-cell infusion. CD19 CAR T-cell therapy with concurrent ibrutinib was well tolerated; 13 patients (68%) received ibrutinib as planned without dose reduction. The 4-week overall response rate using 2018 International Workshop on CLL (iwCLL) criteria was 83%, and 61% achieved a minimal residual disease (MRD)-negative marrow response by IGH sequencing. In this subset, the 1-year overall survival and progression-free survival (PFS) probabilities were 86% and 59%, respectively. Compared with CLL patients treated with CAR T cells without ibrutinib, CAR T cells with concurrent ibrutinib were associated with lower CRS severity and lower serum concentrations of CRS-associated cytokines, despite equivalent in vivo CAR T-cell expansion. The 1-year PFS probabilities in all evaluable patients were 38% and 50% after CD19 CAR T-cell therapy, with and without concurrent ibrutinib, respectively (P = .91). CD19 CAR T cells with concurrent ibrutinib for R/R CLL were well tolerated, with low CRS severity, and led to high rates of MRD-negative response by IGH sequencing.
© 2020 by The American Society of Hematology.
Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen Receptor-Modified T Cells After Failure of Ibrutinib.J Clin Oncol. 2017 Sep 10;35(26):3010-3020. doi: 10.1200/JCO.2017.72.8519. Epub 2017 Jul 17. J Clin Oncol. 2017. PMID: 28715249 Free PMC article. Clinical Trial.
Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL.JCI Insight. 2019 Apr 2;5(9):e122627. doi: 10.1172/jci.insight.122627. JCI Insight. 2019. PMID: 30938714 Free PMC article.
[Ibrutinib combined with CAR-T cells in the treatment of del (17p) chronic lymphocytic leukemia with BCL-2 inhibitor resistance: a case report and literature review].Zhonghua Xue Ye Xue Za Zhi. 2019 Sep 14;40(9):750-754. doi: 10.3760/cma.j.issn.0253-2727.2019.09.008. Zhonghua Xue Ye Xue Za Zhi. 2019. PMID: 31648477 Chinese.
CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL).Ther Adv Hematol. 2015 Oct;6(5):228-41. doi: 10.1177/2040620715588916. Ther Adv Hematol. 2015. PMID: 26425336 Free PMC article. Review.
CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia.Curr Treat Options Oncol. 2016 Jun;17(6):28. doi: 10.1007/s11864-016-0406-4. Curr Treat Options Oncol. 2016. PMID: 27098534 Review.