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    Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma

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    Author
    Weppler, AM; Pattison, A; Bhave, P; De Ieso, P; Raleigh, J; Hatzimihalis, A; Gill, AJ; Balachander, S; Callahan, J; Chua, M; ...
    Date
    2020-01-01
    Source Title
    Journal for ImmunoTherapy of Cancer
    Publisher
    BMJ PUBLISHING GROUP
    University of Melbourne Author/s
    Hicks, Rodney; Sandhu, Shahneen; Tothill, Richard; Balachander, Shiva; Pattison, Andrew; Caneborg, Peter; Chua, Margaret; Au-Yeung, George; McArthur, Grant; Callahan, Jason
    Affiliation
    Medicine and Radiology
    Sir Peter MacCallum Department of Oncology
    Clinical Pathology
    Metadata
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    Document Type
    Conference Paper
    Citations
    Weppler, A. M., Pattison, A., Bhave, P., De Ieso, P., Raleigh, J., Hatzimihalis, A., Gill, A. J., Balachander, S., Callahan, J., Chua, M., Au-Yeung, G., McArthur, G. A., Hicks, R. J., Tothill, R. W. & Sandhu, S. (2020). Clinical, FDG-PET and molecular markers of immune checkpoint inhibitor response in patients with metastatic Merkel cell carcinoma. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 8, (2), BMJ PUBLISHING GROUP. https://doi.org/10.1136/jitc-2020-000700.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/252890
    DOI
    10.1136/jitc-2020-000700
    Abstract
    BACKGROUND: Metastatic Merkel cell carcinoma (mMCC) is an aggressive neuroendocrine malignancy of the skin with a poor prognosis. Immune checkpoint inhibitors (ICIs) have shown substantial efficacy and favorable safety in clinical trials. METHODS: Medical records of patients (pts) with mMCC treated with ICIs from August 2015 to December 2018 at Peter MacCallum Cancer Centre in Australia were analyzed. Response was assessed with serial imaging, the majority with FDG-PET/CT scans. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples was performed. RESULTS: 23 pts with mMCC were treated with ICIs. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 6 pts. Objective responses (OR) were observed in 14 pts (61%): 10 (44%) complete responses (CR) and 4 (17%) partial responses (PR). Median time to response was 8 weeks (range 6 to 12) and 12-month progression-free survival rate was 39%. Increased OR were seen in pts aged less than 75 (OR 80% vs 46%), no prior history of chemotherapy (OR 64% vs 50%), patients with an immune-related adverse event (OR 100% vs 43%) and in MCPyV-negative tumors (OR 69% vs 43%). Pts with a CR had lower mean metabolic tumor volume on baseline FDG-PET/CT scan (CR: 35.7 mL, no CR: 187.8 mL, p=0.05). There was no correlation between PD-L1 positivity and MCPyV status (p=0.764) or OR (p=0.245). 10 pts received radiation therapy (RT) during ICI: 4 pts started RT concurrently (OR 75%, CR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. Overall, 6 pts (26%) had grade 1-2 immune-related adverse events. CONCLUSION: ICIs showed efficacy and safety in mMCC consistent with trial data. Clinical and imaging predictors of response were identified.

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