Serum Marker Helps Predict Response to CAR-T Therapy in Lymphoma

Submitted by admin5 on Fri, 04/28/2017 - 13:47

Patients with relapsed or refractory lymphoma who achieve durable remission after low-dose conditioning chemotherapy and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tend to have high serum levels of a particular protein.

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CAR T-cells targeting CD19 are very active against acute lymphoblastic leukemia, but limited results supporting treatment of lymphoma with CD19 CAR T-cells have been published. Patients with chemotherapy relapsed or refractory lymphoma after autologous stem-cell transplantation have a poor prognosis, and new treatments for such patients are needed. Chemotherapy given before adoptively transferred T-cells has been shown to enhance preventative activity in these cells.

James N Kochenderfer, MD, National Cancer Institute (Bethesda, MD), and colleagues conducted a study to assess the efficacy of CD19 CAR T-cell therapy after chemotherapy in patients with lymphoma. A total of 22 patients with advanced-stage lymphoma received a single dose of CD19 CAR T-cells 2 days after a low-dose chemotherapy conditioning regimen involving cyclophosphamide plus fludarabine. The study was published in the Journal of Clinical Oncology (published online March 14, 2017; doi:10.1200/JCO.2016.71.3024).

Results of the treatment showed an overall remission rate of 73% among the patient sample, with 55% complete remissions and 18% partial remissions. The low-dose chemotherapy conditioning regimen was found to deplete blood lymphocytes and increased serum interleukin-15.

Those patients who achieved remission demonstrated a median peak blood CAR+ cell level of 98/ μL, whereas those patients who did not achieve remission had a median peak blood CAR+ cell level of 15/ μL (= .027). Researchers found that high serum interleukin-15 levels were associated with high peak blood CAR+ cell levels (= .001) and remission of lymphoma (< .001).

Researchers concluded that CD19 CAR T-cells preceded by low-dose chemotherapy induced remission of advanced lymphoma, along with high serum interleukin-15 levels, are associated with the effectiveness of the treatment regimen.

Researchers predict that CD19 CAR T-cells will likely become an important treatment option for patients with relapsed or refractory lymphoma. – Zachary Bessette