Merkel Cell Carcinoma: Promising Treatment With Combination of T cells and PD-1 Blockade

MedicalResearch.com Interview with:
Dr. Kelly Garneski Paulson, MD, PHD
Fred Hutchinson Cancer Research Center
Seattle, WA  

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Merkel cell carcinoma (MCC) is an aggressive skin cancer with increasing impact. Currently, there are more than 2000 new cases of MCC diagnosed each year in the US. Over one third of patients will develop metastatic disease.

Most cases of Merkel cell carcinoma are caused by a virus (Merkel cell polyomavirus). In these cancers, the viral oncoproteins (cancer causing proteins) are highly expressed (exclusively on tumor tissue), immunogenic and are necessary for cancer growth.  These oncoproteins are thus ideal targets for cancer immunotherapy, making MCC a great cancer in which to study and develop immunotherapy.  Indeed, immunotherapies are effective in MCC, with observed response to checkpoint inhibitor mono therapy on the order of 35-55%, although complete responses remain rare.

In our first trial, we treated four patients with metastatic Merkel cell carcinoma with endogenous T cell therapy (ex vivo expanded polyclonal T cells recognizing Merkel cell polyomavirus). One patient developed a complete response, but three patients rapidly progressed. Interestingly, we observed that the patient with the complete response had low levels of PD-1 expression on the virus specific transferred T cells. We thus hypothesized adding adding an immune checkpoint inhibitor (avelumab, anti-PD-L1) to the transferred T cells would be acceptably safe and potentially improve clinical effectiveness.

MedicalResearch.com: What are the main findings?

Response: We then treated four patients with advanced Merkel cell carcinoma with the combination of T cells and avelumab. Safety of this combination was similar to safety of T cells alone, with expected transient lymphopenia and short-duration cytokine release syndrome lasting less than 48 hours and managed on the general ward. All four patients developed objective responses by RECIST 1.1, and three of the patients developed a complete response that was sustained at 12+ months.  Importantly, in patients receiving the combination therapy we were able to demonstrate T cell persistence and function, as well as infused T cell localization preferentially to the tumor (suggesting T cell contributions to the anti tumor effect). We were further able to demonstrate spreading/broadening of the T cell responses, which we believe will help promote long term tumor control.

Although the study is early/small, responses are currently very encouraging, and no unexpected adverse safety signal was seen with the combination of T cells and PD-1 axis blockade.

MedicalResearch.com: What should readers take away from your report?

Response: Cellular immunotherapy, particularly in combination with other immunotherapy agents, is a promising strategy for the treatment of Merkel cell carcinoma and deserving of further study.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: ASCO 2017

Augmentation of adoptive T-cell therapy for Merkel cell carcinoma with avelumab.
Author(s): Kelly Garneski Paulson, Maurizio Perdicchio, Rima Kulikauskas, Felecia Wagener, Candice Church, Kieu-Thu Bui, Natalie Vandeven, Hannah Thomas, Megan McAfee, Natalie Miller, Kevin M. Chin, Zhen Su, Philip D Greenberg, Upendra Parvathaneni, Shailender Bhatia, Paul Nghiem, Aude Chapuis; Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington, Seattle, WA; EMD Serono, Inc., Billerica, MA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; University of Washington Fred Hutchinson Cancer Center, Seattle, WA

http://abstracts.asco.org/199/AbstView_199_185408.html

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

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