CAR T-Cell Therapy in Refractory B-Cell Lymphomas
As reported at the recent American Society of Hematology Annual Meeting & Exposition and in The New England Journal of Medicine, Schuster et al found that chimeric antigen receptor (CAR) T-cell therapy produced responses in a high proportion of patients with B-cell lymphomas refractory to or who had relapsed after previous treatments.
Study Details
This case-series study was conducted at the Hospital of the University of Pennsylvania and included 14 adult patients with diffuse large B-cell lymphoma and 14 patients with follicular lymphoma treated between March 2014 and August 2016. Outcome data are current through May 2017. Patients received an infusion of autologous T cells expressing a CD19-directed CAR (CTL019; 1.00 × 108 to 5.00 × 108 CTL019 cells) at 1 to 4 days after completion of lymphodepleting chemotherapy.
Response Rates
Among the 28 patients, response was observed in 18 (64%), including 7 (50%) with diffuse large B-cell lymphoma and 11 (79%) with follicular lymphoma. Complete remission was observed in 6 patients (43%) with diffuse large B-cell lymphoma and 10 patients (71%) with follicular lymphoma.
CTL019 cells were found to proliferate in vivo and were detectable in blood and bone marrow of both responders and nonresponders. At a median follow-up of 28.6 months, 86% of responders with diffuse large B-cell lymphoma and 89% of responders with follicular lymphoma had a maintained response. All patients achieving complete remission by 6 months remained in remission at 7.7 to 37.9 months (median = 29.3 months) after induction. There was a sustained reappearance of B cells in 8 of 16 patients and improvement in immunoglobulin (Ig) G levels in 4 of 10 patients and IgM levels in 6 of 10 patients at ≥ 6 months and in IgA levels in 3 of 10 patients at ≥ 18 months.
Adverse Events
Severe cytokine-release syndrome occurred in five patients (18%), with no deaths observed. Eleven patients (39%) had treatment-related neurologic toxic effects. Serious encephalopathy occurred in three patients (11%), with two being self-limiting and one being fatal.
The investigators concluded: “CTL019 cells can be effective in the treatment of relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma. High rates of durable remission were observed, with recovery of B cells and immunoglobulins in some patients. Transient encephalopathy developed in approximately one in three patients and severe cytokine-release syndrome developed in one in five patients.”
The study was funded by Novartis and others.
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