September 8, 2016 (HealthDay News)
Researchers identify treatment characteristics that correlate with therapeutic response, toxicity
Immunotherapy with CD19 chimeric antigen receptor (CAR)-modified T cells in a defined CD4+/CD8+ ratio can lead to improved disease response and overall and progression-free survival, according to a study published in the Sept. 7 issue of Science Translational Medicine.
Cameron Turtle, Ph.D., an immunotherapy researcher with the Fred Hutchinson Cancer Research Center in Seattle, and colleagues manufactured CD19 CAR-T cells from defined T cell subsets. The therapy was administered in a 1:1 CD4+/CD8+ ratio of CAR-T cells to 32 adults with relapsed and/or refractory B cell non-Hodgkin’s lymphoma after cyclophosphamide (Cy)-based lymphodepletion chemotherapy with or without fludarabine (Flu).
The researchers found that patients who underwent Cy/Flu lymphodepletion had increased CAR-T cell expansion and persistence, and higher response rates than patients who received Cy-based lymphodepletion without Flu (50 percent complete remission [CR], 72 percent overall response rate [ORR] versus 8 percent CR, 50 percent ORR). Serum biomarkers one day after CAR-T cell infusion correlated with severe cytokine release syndrome and grade ≥3 neurotoxicity, which were observed in 13 and 28 percent of all patients, respectively.
“Immunotherapy with CD19 CAR-T cells in a defined CD4+/CD8+ ratio allowed identification of correlative factors for CAR-T cell expansion, persistence, and toxicity, and facilitated optimization of lymphodepletion that improved disease response and overall and progression-free survival,” the authors write.
Several authors disclosed financial ties to Juno Therapeutics, which contributed funding to the study.
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