Agent Shows Impressive Results for Diffuse Large B-Cell Lymphoma

JCAR017 had promising complete response and objective response rates in treating patients with diffuse large B-cell lymphoma (DLBCL) in a recently presented study.
BY SILAS INMAN @silasinman
PUBLISHED: JUNE 19, 2017
According to updated findings from the core group of the phase 1 TRANSCEND study, treatment with JCAR017 showed a 59 percent complete response (CR) rate and an objective response rate (ORR) or 86 percent for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Findings were presented at the 2017 International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland.

In the study, the CD19-targeted CAR T-cell therapy JCAR017, which consists of a defined cell composition and 4-1BB costimulatory domain, was administered to 67 total patients at the May 4, 2017, data cutoff. The core group presented at ICML included those with de novo and transformed DLBCL and an ECOG performance status of 0 or 1 (44 patients). The core population is the focus of future pivotal studies for JCAR017.

In the core group, after three months of follow-up, the CR rate with JCAR017 was 50 percent and the ORR was 66 percent. Ninety percent of those responding at three months continued to response at six months (9 of 10). Of those with any level of response (38 patients), 97 percent remained alive after a median follow up of 3.2 months. The median overall survival in the full population (which included those with ECOG 2 status) was 4.2 months.

"This is the first multicenter trial of a CD19-directed CAR T cell product with defined composition to deliver potent and durable responses in poor-prognosis subgroups of relapsed/refractory aggressive non-Hodgkin lymphoma," said lead investigator Jeremy S. Abramson, M.D., from Massachusetts General Hospital Cancer Center. "A DLBCL pivotal cohort is planned to open later this year for the core patient population."

In the TRANSCEND study, patients underwent leukapheresis at study entry followed by manufacturing of JCAR017. Efforts are under way to bring the total manufacturing time from apheresis to delivery for JCAR017 to below 21 days, Abramson noted.

Prior to CAR T cell infusion, patients received lymphodepleting fludarabine (30 mg/m2) and cyclophosphamide (300 mg/m2) daily for three days. A modified continual reassessment method was utilized to determine CAR T cell dose level (DL), to avoid potential adverse events (AEs). Two DLs were utilized: 5 x 107 cells (DL1) and 1 x 108 cells (DL2) either as a single-dose or double-dose. Thirty patients got single DL1 (DL1S), 6 got double DL1 (DL1D), and 19 patients received DL2 as a single dose (DL2S).

Across all evaluable patients (55 patients), the median age was 61 years, with 40 percent at leasat 65 years of age. Overall, 40 patients had de novo DLBCL (73 percent), 14 had transformed DLBCL (26 percent), and one patient had grade 3B follicular lymphoma (2 percent). Two patients had central nervous system (CNS) involvement. Seventy-six percent of patients were chemorefractory, and 27 percent had double or triple hit lymphoma. The median number of prior therapies was three (range, 1-11) and 49 percent of patients had received a prior stem cell transplant (allogeneic, 7 percent; autologous, 44 percent).



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