Anti-CD19 CAR T-Cell Treatment Effective in Chemotherapy-Refractory B-Cell Malignancies
In a study reported in the Journal of Clinical Oncology, Kochenderfer et al found that single infusions of autologous T cells expressing an anti-CD19 chimeric antigen receptor (CAR) produced responses in nearly all patients with chemotherapy-refractory CD19-positive B-cell malignancies, including patients with diffuse large B-cell lymphoma.
Study Details
In the study, nine patients with diffuse large B-cell lymphoma and six with indolent B-cell malignancies received a conditioning regimen of cyclophosphamide at a total dose of 120 or 60 mg/kg followed by five daily doses of fludarabine 25 mg/m2 and a single infusion of anti-CD19 CAR T cells 1 day after completing chemotherapy. Due to toxicity, the dose of CAR-positive T cells was reduced from 5×106 to 1×106 cells/kg during the study.
Responses
Of 15 patients, 8 had complete remissions, 4 had partial remissions, 1 had stable disease, and 2 were not evaluable for response (complete or complete remission in 12 of 13 evaluable patients). Of the two patients who were not evaluable for response, one died soon after treatment and one was lost to follow-up due to noncompliance. Complete or partial remission was achieved in each of the six evaluable patients with indolent malignancies, with complete remissions ongoing in three of four patients with chronic lymphocytic leukemia at the time of reporting. Of the seven evaluable patients with diffuse large B-cell lymphoma, four had complete remissions, two had partial remissions, and one had stable disease; at the time of reporting, three complete remissions were ongoing with durations of 9 to 22 months.
Toxicities
Patients experienced numerous grade 3 or 4 toxicities, including fever in 12, hypotension in 4, and confusion or other neurologic toxicities in 6 after infusion of anti-CD19 CAR T cells. However, these toxicities resolved within 3 weeks after infusion. One patient died suddenly due to unknown cause 16 days after infusion.
The investigators concluded: “This is the first report to our knowledge of successful treatment of [diffuse large B-cell lymphoma] with anti-CD19 CAR T cells. These results demonstrate the feasibility and effectiveness of treating chemotherapy-refractory B-cell malignancies with anti-CD19 CAR T cells. The numerous remissions obtained provide strong support for further development of this approach.”
James N. Kochenderfer, MD, of the National Institutes of Health, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the National Cancer Institute and by Kite Pharma through a cooperative research and development agreement with the Surgery Branch of the National Cancer Institute. Steven A. Rosenberg, MD, PhD, reported a consultant or advisory role and research funding from Kite Pharma.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
