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ASCO 2022: PD-1 Inhibitory–Refractory Merkel Cell Carcinoma: Is T-Cell Therapy a Step in the Right Direction?

By: Celeste L. Dixon
Posted: Friday, June 24, 2022

Five HLA-A02 patients with metastatic Merkel cell carcinoma that was refractory to PD-1 inhibitor therapy participated in a trial to test whether adoptive transfer of autologous T cells transduced with Merkel polyomavirus–specific T cells could lead to a clinical response. Although four patients experienced progressive disease, one had a mixed response and a disease-free interval longer than 1 year following local therapy of an isolated site of disease progression, reported Joshua Veatch, MD, PhD, of Fred Hutchinson Cancer Research Center, Seattle, and colleagues in a presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9549).

“The responding patient was the only [one] with class I major histocompatibility complex [MHC] staining on tumor cells prior to treatment. The site of local progression in that patient showed the presence of T-cell receptor transgenic T cells but loss of class I MHC expression,” noted the team.

Specifically, the patients were treated with adoptive transfer of CD62L-positive, CD8+-positive, and CD4-positive autologous T cells transduced with a T-cell receptor targeting an HLA-A0201–restricted Merkel polyomavirus epitope. Also, “two different strategies were used to facilitate T-cell expansion,” explained the investigators. In three patients, prior to T-cell transfer, single-fraction radiation was administered to a subset of lesions, whereas in the other two, prior to the transfer, lymphodepleting chemotherapy with cyclophosphamide and fludarabine was administered. Ultimately, T-cell persistence was lower with the second pretransfer strategy.

What the researchers learned, they reported, is that Merkel polyomavirus–specific transgenic T cells are safe. The cells “traffic to tumor sites and can result in a clinical response, but their clinical activity may be limited by downregulation of class I MHC expression on tumors.” Given that hypothesis, “a future trial will address strategies to increase class I MHC expression on Merkel tumors,” the team announced.

Disclosure: The study authors’ disclosure information can be found at coi.asco.org.


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