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Research in Review

High Response Rates With New Treatment for Aggressive B-Cell Lymphoma

In a recent trial, researchers determined complete response rates in patients with aggressive B-cell lymphomas after treatment with new a CAR T-cell product.

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Researchers found high complete response (CR) rates in patients with heavily pretreated B-cell non-Hodgkin lymphoma (B-NHL) after treating them with the CD19-directed CAR T-cell product JCAR017 in a treatment trial.

The results of the trial were presented today at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

The trial included 28 patients as of November 23, 2016. There were 19 males and nine females in the trial, 25 of whom with diffuse large B-cell lymphoma (DLBCL), two with mantle cell lymphoma (MCL), and one with grade IIIb follicular lymphoma (FL). Patients ranged in age from 37 to 79 years, and the number of prior therapies ranged from one to eight. About 23 patients were refractory to their last chemotherapy, and 16 had undergone a prior transplant.

Treatment included lymphodepletion with fludarabine and cyclophosphamide, followed by JCAR017.

The researchers observed no severe cytokine release syndrome (sCRS), but 10 patients had grade 1 or 2 CRS, of which one patient received tocilizumab. The median onset of CRS was 5 days.

Neurotoxicity occurred in five patients, with four patients developing grade 3 to 4 neurotoxicity; all events resolved in those four patients before follow-up. Median onset of neurotoxicity was 11 days.

A total of 20 patients treated at DL1 (5×107 cells) demonstrated a relative risk of 80%, with 60% achieving CR, according to the researchers. The researchers detected JCAR017 at 3 and 6 months in patients who responded to the treatment, including those who relapsed. The researchers also found higher mean peak levels in patients with durable response at 3 months.

Four patients had died after disease progression, but no deaths were related to JCAR017.

“Treatment with JCAR017 results in high CR rate in patients with heavily pretreated R/R DLBCL,” the researchers concluded. “Relapses can occur despite persistence of JCAR017, suggesting tumor immune evasion mechanisms may contribute to relapse. Observed toxicities are manageable and occurred at rates lower than those reported for other CD19-directed CAR T cell products.”—Christina Vogt