Autologous chimeric antigen receptor (CAR) T cells are rapidly changing the treatment landscape for chronic lymphocytic leukemia (CLL). According to research published in Clinical Lymphoma, Myeloma & Leukemia, the future of CLL therapy may lie in combining CAR T cells with costimulatory molecules and adjunctive therapies.1

Anthony R Mato, MD, of the Center for Chronic Lymphocytic Leukemia at the Abramson Cancer Center at the University of Pennsylvania in Philadelphia, and colleagues analyzed the current state of CAR T therapy in CLL and concluded that as technology progresses and experience increases, there is significant potential for improving outcomes in patients with CLL. “Although most studies of CAR T cells for CLL have been directed against cluster of differentiation (CD)19, other approaches are in development,” wrote the authors. “Data using an anti-CD20 CAR have shown limited activity in patients with lymphoma, and future iterations of this approach are likely to be applied in CLL.”

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Other antigens, such as CD23, R0R1, and FCm, are also being investigated in clinical trials. In addition, the Bruton’s tyrosine kinase inhibitor ibrutinib is being assessed as a therapeutic option following allogeneic stem cell transplant and CAR T therapies. “In my opinion, CAR T will become a treatment option for patients with relapsed refractory CLL not too far from now,” said Henry Chi Hang Fung, MD, vice chair of the department of hematology/oncology at the Fox Chase Cancer Center in Philadelphia, Pennsylvania.

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Dr Mato and colleagues noted that agents such as ibrutinib, venetoclax, and idelalisib have demonstrated significant benefits for patients with CLL, but alternatives are needed for patients who do not respond to these treatments. Dr Fung concurred, stating that although there have been dramatic improvements in the standard of care in the past 5 years, there is still large unmet medical need. He added that therapies requiring potentially lifelong treatment with ensuing financial toxicities raise further concern.

What Is Known So Far

CAR T therapy, a kind of adoptive cellular therapy, involves extraction of T cells from a patient’s blood, insertion of the CAR gene into the cells’ genome, replication of the resulting CAR-modified T cells, and reintroduction of the CAR T cells into the patient’s bloodstream. In 2011, successful use of CAR T cells directed against CD19 was described for the first time.2 Since then, 7 additional studies on the use of CAR T therapy in CLL have been published, and several other therapeutic approaches have been investigated.