In a letter to the New England Journal of Medicine, a Massachusetts General Hospital (MGH) research team reports a remarkable treatment response in a patient participating in a clinical trial of a novel immune-system-based cancer therapy. Treatment with an investigational CAR T-cell therapy induced complete remission of a brain metastasis of the difficult-to-treat tumor diffuse large-B-cell lymphoma (DLBCL), which had become resistant to chemotherapy – the first report of a response to CAR T-cells in a central nervous system lymphoma.

In addition, when a subcutaneous tumor began to recur two months after CAR T-cell therapy and a surgical biopsy was performed, the CAR T-cells spontaneously re-expanded and the tumor again went into remission, and phenomenon that had not previously been reported. While the patient eventually relapsed and died more than a year after CAR T-cell therapy, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” explains Jeremy Abramson, MD, of the MGH Cancer Center, lead author of the letter in the Aug. 24 NEJM. “In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.

Chimeric antigen receptor (CAR) T-cell therapies utilize a patient’s own T cells that have been genetically engineered to bind to a specific antigen on target cancer cells. This clinical trial sponsored by Juno Therapeutics is testing JCAR017, which targets the CD19 protein expressed on most B-cell leukemias and lymphomas. The most common type of non-Hodgkin lymphoma in adults, DLBCL is an aggressive cancer that can develop in many types of tissue.

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