Chronic lymphocytic leukemia (CLL) is a type of cancer that starts from lymphocytes in the bone marrow. 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 CAR T-cell immunotherapy developed at Seattle's
Fred Hutchinson Cancer Research Center.
Fred Hutch researchers presented their findings at the American Society of Hematology
Annual Meeting and Exposition in San Diego.
‘Chronic lymphocytic leukemia patients who had exhausted most traditional treatments saw their tumors shrink or even disappear after an infusion of a highly targeted, experimental CAR T-cell immunotherapy.’
Almost all of the 24 patients in the study had cancer that had
advanced despite treatment with a newly approved drug called ibrutinib -
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 Dr.
Cameron Turtle, a hematologist/oncologist in the Clinical Research
Division at Fred Hutch who co-leads the trial with colleagues Drs. David
Maloney and Stanley Riddell.
Turtle's presentation will focus 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," 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.
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 each patient's blood. A modified virus delivers genetic
instructions into the cells for making a CAR, or 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.
CD19 CAR T-cell studies at Fred Hutch are unique because the
researchers engineer specific subsets of cells from the patient and
formulate the cell product to be uniform. By creating CAR T-cells with a
defined composition of T cell subsets, the researchers can improve the
link between the dose of cells a patient receives and what they
experience afterward - not just benefits, but also potential side
Patients in the trial are seen at Seattle Cancer Care Alliance, Fred Hutch's clinical care partner.