Review
Driving Out Chronic Lymphocytic Leukemia With CAR T Cells

https://doi.org/10.1016/j.jtct.2021.10.005Get rights and content
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Highlights

  • High-risk chronic lymphocytic leukemia (CLL) continues to pose a therapeutic challenge.

  • Responses to chimeric antigen receptor (CAR) T cell therapy have been impressive even in high-risk CLL.

  • If granted Food and Drug Administration approval, CAR T cell therapy could be considered in pathway inhibitor failure.

  • Off-the-shelf CAR T cell products offer the option of more readily available therapies.

ABSTRACT

Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the Western hemisphere. The recent availability of novel targeted therapies, namely Bruton's tyrosine kinase, phosphoinositide-3 kinase, and BCL-2 inhibitors, have revolutionized the treatment algorithm for CLL but have not yet resulted in cure. Advances in the field of immuno-oncology and T cell engineering brought chimeric antigen receptor (CAR) T cell therapy from the laboratory to the clinic for treatment of B cell lymphoid malignancies and has improved the disease response and survival outcomes of various types of relapsed and/or refractory B cell lymphomas. While acknowledging that there are no approved CAR T cell therapies for CLL at this time, in this comprehensive review we explore novel targets for CAR T cell therapy in CLL and highlight the promising results of CAR T cell trials reported to date. Furthermore, we shed light on future areas of development, including multitarget CAR T cell products for this disease.

Key Words

Chronic lymphocytic leukemia
Chimeric antigen receptor T cell therapy
Novel antigen target
Response rate
Survival

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Financial disclosure: See Acknowledgments on page 15.