Conference Coverage

CAR T-cell studies dominate ongoing cellular therapy trials


 

EXPERT ANALYSIS FROM THE NCCN HEMATOLOGIC MALIGNANCIES CONGRESS

– The cell therapy landscape increasingly involves strategies beyond chimeric antigen receptor (CAR) T-cell therapy, but those studies still predominate among investigational trials, according to Frederick L. Locke, MD, of Moffitt Cancer Center in Tampa.

Researchers are looking at CAR T-cell therapy for earlier lines of treatment, especially in patients with aggressive lymphomas, Dr. Locke said at the annual congress on Hematologic Malignancies held by the National Comprehensive Cancer Network.

Of 753 trials examining cell therapies and listed at ClinicalTrials.gov as of March 30, 2018, about half (404) were CAR T-cell therapies. The others included T-cell receptor therapies, tumor infiltrating lymphocyte therapies, dendritic cell vaccines, and natural killer cell–based therapies, according to an article in Nature Reviews.

“The development isn’t just here in the United States,” Dr. Locke said. “It’s really global. We see a lot of activity in Europe, but also in China. We’re seeing medical advances across the world through molecular biology and gene engineering of T cells and other immune cells which can be adoptively transferred into patients.”

That activity includes studies seeking to move CAR T-cell therapy earlier in the treatment paradigm for some diseases, he added. “CAR T-cell therapy in non-Hodgkin lymphoma is really beginning a paradigm shift, at least in my mind.”

Several large, randomized trials that are now comparing CD19 CAR T-cell therapy with second-line standard-of-care therapies for patients with aggressive B-cell lymphomas. Among those trials is ZUMA-7, a phase 3, randomized trial comparing axicabtagene ciloleucel with standard-of-care treatment in patients with relapsed or refractory diffuse large B-cell lymphoma.

While prognosis remains poor for relapsed or progressing aggressive B-cell lymphomas treated with chemotherapy, data to date suggest CAR T-cell therapy produces durable, long-term remissions in about 40% of patients at “a year out and counting,” Dr. Locke said.

He presented a proposed treatment algorithm that included R-CHOP chemotherapy up front and CAR T-cell therapy in later lines of treatment, an approach that Dr. Locke speculated could result in a cure rate of perhaps 80% in large-cell lymphomas.

Encouraging longer-term data is emerging, with some patients with aggressive T-cell lymphomas now without recurrence for 5 years or more following a single infusion of CAR T-cell therapy, he said.

Dr. Locke reported a financial disclosure related to Cellular Biomedicine Group.

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