In a small, early-phase trial, a high percentage of patients who had exhausted most traditional treatments for chronic lymphocytic leukemia saw their tumors shrink or even disappear after an infusion of a highly targeted, experimental CD19-targeting chimeric antigen receptor (CAR) T-cell immunotherapy developed at Seattle's Fred Hutchinson Cancer Research Center. The Fred Hutch scientists presented their findings at the American Society of Hematology Annual Meeting and Exposition in San Diego.

Almost all of the 24 patients in the study had cancer that had advanced despite treatment with a newly approved drug, ibrutinib. Most patients also had chromosomal markers in their leukemia cells that put them at high risk, “predictors of a bad response to most standard therapies,” said Cameron Turtle, M.D., a hematologist/oncologist in the Clinical Research Division at Fred Hutch.

Dr. Turtle's presentation focused on the results in a subgroup of patients who received the CAR T-cell infusion using preferred chemotherapy and CAR T-cell doses that evolved from recent trial data. Fourteen of the 19 restaged patients experienced a partial or complete regression of the disease in their lymph nodes. Of the 17 who had leukemia in their marrow when they enrolled in the trial, 15 saw the marrow become cancer-free after receiving CAR T-cells.

“These are all heavily pretreated patients who've gone through many previous therapies,” Dr. Turtle said. “It's very pleasing to see patients with refractory disease respond like this.”

Participants with the highest number of CAR T-cells in their blood after infusion were the most likely to have their disease disappear from bone marrow after CAR T-cell infusion. Side effects included high fevers, due to activation of CAR T-cells, and neurologic symptoms. Although one patient died from severe toxicity, the side effects experienced by other patients in the study were temporary. 

Dr. Turtle and his colleagues also identified certain biomarkers in patients' blood the day after infusion that were associated with the later development of the most severe toxicities. The researchers hope these biomarkers could eventually lead to tests to predict and mitigate the most serious side effects.