Team reports first response of central nervous system tumor to CAR T-cells

In a letter to the New England Journal of Medicine, a Massachusetts General Hospital (MGH) analysis staff reports a exceptional remedy response in a affected person collaborating in a medical trial of a novel immune-system-based most cancers remedy. Treatment with an investigational CAR T-cell remedy induced full remission of a mind metastasis of the difficult-to-treat tumor diffuse large-B-cell lymphoma (DLBCL), which had develop into 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 started to recur two months after CAR T-cell remedy and a surgical biopsy was carried out, the CAR T-cells spontaneously re-expanded and the tumor once more went into remission, and phenomenon that had not beforehand been reported. While the affected person ultimately relapsed and died greater than a yr after CAR T-cell remedy, the mind tumor by no means 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 writer of the letter within the Aug. 24 NEJM. “In addition, all out there CAR T-cell trials have excluded sufferers with central nervous system involvement. This end result has implications not just for secondary DLBCL like this case but in addition for main central nervous system lymphoma, for which remedy choices are equally restricted after relapse and few patents are cured.

Chimeric antigen receptor (CAR) T-cell therapies make the most of a affected person’s personal T cells which were genetically engineered to bind to a selected antigen on track most cancers cells. This medical trial sponsored by Juno Therapeutics is testing JCAR017, which targets the CD19 protein expressed on most B-cell leukemias and lymphomas. The commonest sort of non-Hodgkin lymphoma in adults, DLBCL is an aggressive most cancers that may develop in many sorts of tissue.

This affected person was a 68-year-old lady with DLBCL that had not responded both to typical chemotherapies or to a stem-cell transplant, a state of affairs that often leads to a life expectancy of lower than six months. After enrolling within the research—a part 1 trial designed to examine the security and antitumor exercise of JCAR017 – -she was discovered to have new lesion in the correct temporal lobe of her mind.

One month after the research remedy—which includes chemotherapy adopted by intravenous infusion of JCAR017—follow-up imaging confirmed full remission of the mind lesion. The subcutaneous lesion that recurred two months later disappeared after the biopsy with no additional remedy. Blood testing confirmed an enlargement within the numbers of CD19-targeted CAR T-cells that coincided with the tumor’s regression. While re-expansion of CAR T-cells has been reported in response to different immunotherapy medicine, that is the first report of such a response to a biopsy.

“Typically the drugs we use to fight cancer and other diseases wear off over time,” Abramson explains. “This spontaneous re-expansion after biopsy highlights this as one thing solely totally different, a ‘dwelling drug’ that may re-expand and proliferate in response to biologic stimuli.” He and his co-authors notice that discovering the mechanisms behind the reactivation of CAR T-cells might additional increase their efficacy.

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More info:
Jeremy S. Abramson et al, Anti-CD19 CAR T Cells in CNS Diffuse Large-B-Cell Lymphoma, New England Journal of Medicine (2017). DOI: 10.1056/NEJMc1704610

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