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CAR T-Cell Therapy an Option for Aggressive Non-Hodgkin Lymphoma

Anti-CD19 CAR T-cell therapy may benefit patients with aggressive B-cell non-Hodgkin lymphoma who have relapsed or are refractory to standard therapy.

CHICAGO-Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy may benefit patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who have relapsed or are refractory to standard therapy, according to a new study presented (abstract 7513) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago. 

Jeremy Abramson, MD, who is an Assistant Professor of Medicine at Harvard Medical School and the Clinical Director of the Lymphoma Program at Massachusetts General Hospital in Boston, is heading up an ongoing large multicenter phase I study of the anti-CD19 CAR T-cell product JCAR017 and reported results on the first 55 evaluable chemotherapy-refractory diffuse large B-cell lymphoma patients (DLBCL). JCAR017 is a second-generation, CD19-directed, 4-1BB CAR T-cell product. It is comprised of CD8 and CD4 CAR T cells.

All 55 patients in this current analysis had a median of 3 prior regimens and approximately 50% had failed a prior stem cell transplant. The median age was 61 years (range: 29–82 years). Abramson said 76% had chemotherapy-refractory disease and 27% had double-hit or triple-hit cytogenetics. 

“Our best overall response rate in this highly refractory population was 76%, with a complete remission rate of 52%. The majority of responses have been durable at last follow-up, though follow-up remains short. The treatment was very well tolerated with only 2% of patients having severe cytokine release syndrome [CRS], and 16% having severe neurotoxicity, both of which were reversible,” Abramson told OncoTherapy Network.

This is the first CAR T-cell multicenter trial to treat poor prognosis subgroups with relapsed or refractory aggressive NHL. The researchers found high response rates, with good durability at 3 months. Abramson noted that this is a heavily pretreated population with a poor prognosis. He said this therapy is salvaging patients previously considered unsalvageable.

“Chemotherapy-refractory DLBCL is an unmet medical need with standard therapies, all of which produce very low rates of complete response and virtually no durable remissions. We report high complete response rates with encouraging durability in patients with chemotherapy-refractory disease, including double- and triple-hit lymphomas, and patients who have failed stem cell transplant,” explained Abramson.

The researchers found that an increased dose of JCAR017 was associated with higher median levels of CD8-positive and CD4-positive CAR-positive T cells in peripheral blood without an increase in CRS and neurotoxicity. In addition, it appears there is a possible relationship between dose and durable response.

“The predominant toxicity with CAR T-cell therapies are cytokine release syndrome and neurotoxicity, but rates of severe CRS and neurotoxicity are quite low in our study, and are virtually always reversible. We will be opening a pivotal dose expansion of this study later this year,” said Abramson.