Andrea Forschner1, Franz-Joachim Hilke2, Irina Bonzheim3, Axel Gschwind2, German Demidov2, Teresa Amaral1,4, Stephan Ossowski2,5, Olaf Riess2,5, Christopher Schroeder2, Peter Martus6, Bernhard Klumpp7, Irene Gonzalez-Menendez3, Claus Garbe1, Heike Niessner1, Tobias Sinnberg1. 1. Center for Dermatooncology, Department of Dermatology, University Hospital Tübingen, 72076 Tübingen, Germany. 2. Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, 72076 Tübingen, Germany. 3. Institute of Pathology and Neuropathology, University Hospital Tübingen, 72076 Tübingen, Germany. 4. Portuguese Air Force Health Care Direction, 1649-020 Lisbon, Portugal. 5. German DFG NGS Competence Center, NCCT, 72076 Tübingen, Germany. 6. Institute for Clinical Epidemiology and applied Biostatistics (IKEaB), 72076 Tuebingen, Germany. 7. Institute for Radiology, Rems-Murr-Kliniken, 71364 Winnenden, Germany.
Abstract
BACKGROUND: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. METHODS: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients` responses to ICI and survival. RESULTS: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of >50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or <1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. CONCLUSIONS: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.
BACKGROUND:Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. METHODS: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients` responses to ICI and survival. RESULTS: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of >50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or <1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. CONCLUSIONS: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.
Authors: Nicholas D Klemen; Sinchun Hwang; Martina Bradic; Evan Rosenbaum; Mark A Dickson; Mrinal M Gounder; Ciara M Kelly; Mary L Keohan; Sujana Movva; Katherine A Thornton; Ping Chi; Benjamin A Nacev; Jason E Chan; Edmund K Bartlett; Allison L Richards; Samuel Singer; Mark T A Donoghue; William D Tap; Sandra P D'Angelo Journal: Clin Cancer Res Date: 2022-03-01 Impact factor: 12.531
Authors: Sara S Bernardes; Ingrid Ferreira; David E Elder; Aretha B Nobre; Héctor Martínez-Said; David J Adams; Carla Daniela Robles-Espinoza; Patricia A Possik Journal: J Pathol Clin Res Date: 2021-07-02