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Anti-CD19 CAR T cells show promise in chemotherapy-refractory DLBCL
An infusion of anti-CD19 chimeric antigen receptor T cells induced remission in the majority of patients with chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies, according to study results.
“[There has been a] great need for improved therapies for patients with chemotherapy-refractory diffuse large B-cell lymphoma (DLBCL),” James N. Kochenderfer, MD, of the Experimental Transplantation and Immunology Branch at the NCI, told
James N. Kochenderfer
Kochenderfer and colleagues sought to evaluate the safety and efficacy of autologous T cells modified to express an anti-CD19 chimeric antigen receptor (CAR) in 15 patients with advanced B-cell malignancies. Nine patients had DLBCL, two had indolent lymphomas and four had chronic lymphocytic leukemia.
All patients received cyclophosphamide and fludarabine chemotherapy prior to an infusion of the anti-CD19 CAR T cells.
Seven patients with DLBCL were evaluable at the time of the analysis. Four of these patients achieved complete remission, and three of those four had responses ongoing for 9 to 22 months at the time of the analysis. Two patients with DLBCL achieved partial remission and one achieved stable disease.
All six patients with indolent lymphomas or CLL achieved a complete or partial remission.
Researchers noted the peak level of CAR-positive blood cells varied among patients, from nine CAR-positive cells/microliter to 777 CAR-positive cells/microliter. These levels peaked from 7 to 17 days post-infusion.
Adverse events after infusion of the CAR T cells included grade 3 to grade 4 fever, hypotension, delirium and other neurological toxicities. However, these toxicities were transient and resolved within 3 weeks.
One patient died 16 days after infusion. Although the cause of death was unknown, researchers suspect cardiac arrhythmia due to a lack of cytokine-release toxicities and the presence of a modestly decreased left ventricular ejection fraction and sinus tachycardia.
“This is the first report indicating that anti-CD19 CAR T cells have activity against chemotherapy-refractory DLBCL, the treatment is feasible in this patient population and that these genetically modified autologous T cells might play an important role in the treatment of DLBCL in the future,” Kochenderfer said.
Disclosure: One researcher reports a consultant/advisory role with and research funding from Kite Pharma.