David Maloney, MD, PhD, professor of medicine, Division of Oncology, University of Washington, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the success and challenges of chimeric antigen recptor (CAR) T-cell therapy in hematologic malignancies.

One of the challenges with CAR T cells is they are directed against a single target, says Maloney, but in some cases, tumors that have lost the targeted antigen can escape. An optional solution would be to use a second target.

According to Maloney, there are ongoing trials of targeting CD22 and CD20, as both can be combined in the same molecule. Just as you would treat a serious infection with antibiotics to prevent resistance, there may be a possibility to treat with 2 different CAR T-cell therapies, Maloney adds.

Currently, there are 2 FDA approvals of CAR T-cell therapies in the hematologic malignanices treatment paradigm. The first FDA approval of a chimeric antigen receptor CAR T-cell therapy was in August 2017, when tisagenlecleucel (Kymriah) was approved for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refectory or in second or later relapse.

The FDA also approved a second CAR T-cell therapy, the CD19-directed axicabtagene ciloleucel (Yescarta) as a treatment for adults with relapsed or refractory non-Hodgkin lymphoma.

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Dr. Maloney on Targets for CAR T-Cell Therapy

David Maloney, MD, PhD, professor of medicine, Division of Oncology, University of Washington, Clinical Research Division, Fred Hutchinson Cancer Research Center, discusses the preliminary safety data of the chimeric antigen receptor (CAR) T-cell product, JCAR017, in relapsed/refractory aggressive B-cell lymphoma.

JCAR017 is directed against CD19 and is in multicenter clinical trials for patients with aggressive large B-cell lymphoma. The product is different from other CAR T cells since it targets a selected population, explains Maloney.

According to Maloney, being able to give the T cells in a defined mixture of CD4 and CD8 cells creates a better relationship between the dose response and the dose toxicity.

David Maloney, MD, PhD

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