Immune Checkpoint Inhibitors May Increase Response to CAR-T Therapy in ALL

Submitted by admin5 on Fri, 05/19/2017 - 14:44

Pembrolizumab improves response to chimeric antigen receptor (CAR) T-cell treatments in pediatric patients with B-cell relapsed acute lymphoblastic leukemia (ALL), according to research that will be presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).

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CD-19 antigen-targeting CAR-T cells have demonstrated complete response in 70% to 95% of pediatric cases of B-cell ALL. However, some patients with this disease do not respond to CAR T-cell expansion and may even relapse from CAR T-cell proliferation and persistence. A programmed cell death protein-1 (PD-1) checkpoint pathway inhibitor could potentially help improve CAR T-cell expansion, function, and persistence.

Shannon L Maude, MD, PhD, Cancer Immunotherapy Program, Children’s Hospital of Philadelphia (PA), and colleagues conducted a study to assess the relationship of PD-1 inhibitors and CAR T-cell therapy in pediatric patients with B-cell ALL. Researchers sampled 4 children with relapsed ALL previously treated with murine or humanized anti-CD19 CAR T-cells to receive 1-3 doses of the PD-1 inhibitor pembrolizumab. These patients exhibited partial response, no response, or prior history of poor CAR T-cell persistence from CAR T-cell infusion after a follow-up range of 2 weeks to 2 months.

Three of the patients received humanized anti-CD19 CAR T-cells for relapse after prior murine anti-CD19 CAR T-cells. The fourth patient exhibited extramedullary involvement after 4 weeks post-murine anti-CD19 CAR T-cell infusion despite marrow remission.

Results of the study showed that pembrolizumab increased or prolonged detection of circulating CAR T-cells in all 4 patients, 2 of whom demonstrated objective response after pembrolizumab administration. Additionally, pembrolizumab proved to be well tolerated in the patient population, as only a slight fever was reported in 2 of the patients and no autoimmune toxicities were observed.

According the authors, results of the study indicate that pembrolizumab can be safely combined with CAR T-cell therapy for pediatric patients with B-cell ALL. The PD-1 inhibitor helps increase or prolong CAR T-cell detection and may result in objective responses to treatment.

Authors concluded that further investigation is needed to validate that immune checkpoint inhibitors may impact response to CAR T-cell therapy.—Zachary Bessette