Engineered CAR T Cells Achieve Remissions in Diffuse Large B-cell Lymphoma
NEW ORLEANS—Infusions of autologous T cells genetically modified to express a chimeric antigen receptor (CAR) that targets B-cell antigen CD19 were associated with at least partial remissions in 12 of 15 patients with chemotherapy-refractory diffuse large B-cell lymphoma (DLBCL), researchers reported at the 55th American Society of Hematology Annual Meeting and Exposition.
“These results demonstrate the feasibility of treating patients with chemotherapy-refractory B-cell malignancies by using autologous anti-CD19 CAR T cells,” reported James Kochenderfer, MD, of the National Cancer Institute's Experimental Transplantation and Immunology Branch in Bethesda, MD, and coauthors. “The numerous remissions obtained should encourage further development of this approach.”
Results for the initial nine participants were previously reported; the new report described results for 15 subsequently enrolled patients who were administered single-infusion anti-CD19-CAR T cells that had been produced using a new 10-day culture process, the coauthors said.
“We treated 15 patients, including nine patients with chemo-refractory large cell lymphomas, by administering chemotherapy followed by anti-CD19 CAR T cells,” Dr. Kochenderfer reported. “Overall 12 of 13 evaluable patients obtained a [partial remission (PR)] or [complete remission (CR)].”
Participants did not receive exogenous interleukin-2, but were administered cyclophosphamide plus fludarabine (25 mg/m2 daily for 5 days) prior to administration of the anti-CD19-CAR T-cell infusion. An average of 70.5% of infused T cells expressed the CAR.
“This is the first report of successful treatment of chemotherapy-refractory primary mediastinal B-cell lymphoma (PMBCL) and DLBCL not otherwise specified with anti-CD19-CAR T cells,” Dr. Kochenderfer said. “All of the nine treated patients with either PMBCL or DLBCL were chemotherapy-refractory and six of these nine patients obtained either a CR or PR on this trial.”
Peak blood levels of CAR gene-harboring cells ranged from 2.3% to 66.5% of blood mononuclear cells, they reported.
Acute post-infusion toxicities included fever, hypotension and delirium. Toxicities “resolved in less than 3 weeks after the cell infusion and were temporarily associated with elevated serum interleukin-6 and interferon gamma levels in most patients,” the coauthors noted. One patient died suddenly of unknown causes at 16 days post-infusion.