©ASCO/Todd Buchanan
CHICAGO—Infusion of autologous CD19-targeted chimeric antigen receptor (CAR)-modified T cells appears to have promising anti-tumor activity and be well-tolerated as a consolidation to frontline chemotherapy in patients with high-risk chronic lymphocytic leukemia (CLL), researchers report.
In a phase 1 trial, the modified T cells benefitted 43% of patients, including 1 who achieved a complete response and 2 who achieved marrow responses only.
Jae Park, MD, of Memorial Sloan-Kettering Cancer Center in New York, reported the findings at the 2014 ASCO Annual Meeting as abstract 7020.
Dr Park and colleagues enrolled 7 CLL patients who had detectable minimal residual disease after achieving either a partial or complete response following 6 cycles of pentostatin, cyclophosphamide, and rituximab.
Patients then received cyclophosphamide conditioning therapy, followed by 3 escalating doses of CAR T cells in 3 dose cohorts.
Six patients had unmutated IgHV, and 2 patients had del 11q. Four patients had palpable lymphadenopathy, including 1 patient with bulky lymph nodes, prior to T-cell infusion.
After a median follow-up of 11 months, 1 patient achieved a complete response, and 2 patients achieved complete responses in the bone marrow but had progressive disease in the lymph nodes.
Three patients achieved a partial response, and 1 patient had progressive disease, but this patient had rapidly rising absolute lymphocyte count at the time of T-cell infusion, Dr Park noted.
The investigators observed no dose-limiting toxicity. Mild and self-limiting cytokine release syndrome occurred in 3 patients.
“There was a positive correlation between the development of cytokine release syndrome and the CAR T-cell persistence,” Dr Park said.
“Our findings suggest that the CD19-targeted CAR T cells are more effective in eradicating disease in the marrow versus lymph nodes,” he added. “And further studies are being conducted to better understand the mechanism of resistance.”
ASCO discussant Veronika Bachanova, MD, of the University of Minnesota, noted that all previous studies of CAR T-cell therapy in CLL were conducted with relapsed/refractory patients.
“The novelty of this study,” she commented, “is the use of CAR T cells upfront.”
She noted that it can take as long as 8 months to develop the CAR T cells for therapy, adding that “the vector design is of critical importance, since inhibitory signals influence therapy.”
