Very first response of central jumpy system tumour to CAR T-cells reported
In a letter to the Fresh England Journal of Medicine, a Massachusetts General Hospital (MGH) research team reports 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 accomplish remission of a brain metastasis of diffuse large-B-cell lymphoma (DLBCL), which had become resistant to chemotherapy — the very first report of a response to CAR T-cells in a central jumpy system lymphoma.
In addition, when a subcutaneous tumour 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 tumour again went into remission.
While the patient eventually relapsed and died more than a year after CAR T-cell therapy, the brain tumour never recurred.
"Brain involvement in DLBCL carries a grave prognosis, and the capability to induce a accomplish and durable response with conventional therapies is infrequent," explains Jeremy Abramson, MD, of the MGH Cancer Center, lead author of the letter in the NEJM. "In addition, all available CAR T-cell trials have excluded patients with central jumpy system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central jumpy system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured."
Chimeric antigen receptor (CAR) T-cell therapies utilise a patient's own T cells that have been genetically engineered to truss to a specific antigen on target cancer cells.
This clinical trial sponsored by Juno Therapeutics is testing JCAR017, which targets the CD19 protein voiced on most B-cell leukaemias 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.
This patient was a 68-year-old woman with DLBCL that had not responded either to conventional chemotherapies or to a stem-cell transplant, a situation that usually leads to a life expectancy of less than six months.
After enrolling in the probe — a phase one trial designed to investigate the safety and anti-tumour activity of JCAR017 – -she was found to have fresh lesion in the right temporal lobe of her brain.
One month after the investigate treatment — which involves chemotherapy followed by intravenous infusion of JCAR017 — follow-up imaging demonstrated finish remission of the brain lesion.
The subcutaneous lesion that recurred two months later disappeared after the biopsy with no further treatment.
Blood testing demonstrated an expansion in the numbers of CD19-targeted CAR T-cells that coincided with the tumour's regression.
While re-expansion of CAR T-cells has been reported in response to other immunotherapy drugs, this is the very 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 therapy as something entirely different, a 'living drug' that can re-expand and proliferate in response to biologic stimuli."
He and his co-authors note that discovering the mechanisms behind the reactivation of CAR T-cells could further augment their efficacy.