Adding Targeted Therapy Improves CAR-T Response Rates in CLL

Submitted by admin5 on Thu, 06/15/2017 - 15:24

Researchers report significantly improved response rates in patients with chronic lymphocytic leukemia (CLL) treated with concurrent targeted therapy and chimeric antigen receptor T-cell (CAR-T) therapy.

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Anti-CD19 CAR T-cell immunotherapy alone has shown to induce durable complete tumor responses between 25% and 45% in patients with CLL. Pre-clinical research has indicated that combining this immunotherapy with ibrutinib could potentially produce an effective treatment.

Saar Gill, MD, PhD, University of Pennsylvania, and colleagues conducted a study to examine the effects of a CAR-T and ibrutinib combination regimen in patients with CLL. Adult patients who had not achieved a complete treatment response after receiving ibrutinib for 6 months or more were enrolled in the trial. To date, the study has included 10 patients with high-risk CLL who took ibrutinib,  9 of whom have been evaluated for response rates prior to and concurrent with anti-CD19 CAR T-cell immunotherapy.

Bendamustine or fludarabine and cyclophosphamide were used for lymphodepletion 1 week before treatment. During the trial, patients received CAR T-cells and ibrutinib. The researchers used flow cytometry and next-generation deep sequencing for IGH-gene rearrangement to measure marrow CLL burden. Additionally, radiographic evaluations of lymph nodes and the spleen were performed via computed tomography.

Early results of the study were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual meeting in Chicago, Illinois, earlier this month.

According to the researchers, 8 of 9 patients had no CLL in the marrow by flow or minimal residual disease at a median follow-up of 6 months. Ultimately, 89% of patients on the combination demonstrated complete responses with minimal residual disease negativity in the marrow. Five patients had complete responses in the spleen, and 2 patients experienced partial responses and stable disease.

The treatment was generally well-tolerated among patients, despite 9 patients having developed cytokine release syndrome (grade 1/2 in eight patients and grade 3 in one patient). Treatment for cytokine release syndrome was not necessary for any of the patients.

For future studies, researchers plan to treat 25 patients with the combination.

“Longer follow-up will reveal the durability of these results and could support evaluation of a first-line combination approach in an attempt to obviate the need for chronic therapy,” the researchers concluded.—Christina Vogt