ASH 2016: CD19-Targeting CAR T-Cell Immunotherapy Yields High Response Rates in Treatment-Resistant CLL
In a small, early phase trial, a high percentage of patients who had exhausted most traditional treatments for chronic lymphocytic leukemia (CLL) saw their tumors shrink or even disappear after an infusion of a highly targeted, experimental chimeric antigen receptor (CAR) T-cell immunotherapy developed at Fred Hutchinson Cancer Research Center. These findings were presented by Turtle et al at the 58th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego (Abstract 56).
Almost all of the 24 patients in the study had cancer that had advanced, despite treatment with ibrutinib (Imbruvica)—an ominous indicator for patient survival. 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, MBBS, PhD, FRACP, FRCPA, a hematologist/oncologist in the Clinical Research Division at Fred Hutch and co-leader of the trial.
Study Findings
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. Of the 19 restaged patients, 14 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.
Side Effects of CD19 CAR T Cells
In a separate poster presentation, the researchers shared their findings in a detailed characterization of the side effects of CD19 CAR T cells (Abstract 1852). Dr. Turtle and his colleagues 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.
CAR T-cell therapy is accomplished by engineering T cells extracted from the patient's blood. A modified virus delivers genetic instructions into the cells for making a chimeric antigen receptor—a synthetic molecule that allows T cells to recognize and kill cells bearing a particular target. In this case, the target is CD19, a molecule found on the surface of certain blood cells, including CLL cells, and the T cells are a carefully selected, one-to-one combination of two functionally different subsets if T cells. After the CAR T cells are grown in the lab and the patient has received chemotherapy, the new CAR T cells are infused back into the patient.
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