Clinical aspects of immunotherapy and targeted therapy of advanced melanoma

Geukes Foppen, M.H. (2018)

Doctoral Thesis

This thesis focused on different aspects of melanoma treatment with immunotherapy and targeted therapy. In chapter 2 we search for biomarkers that could be associated with overall survival in patients treated with ipilimumab. In chapter 3 we describe diarrea, a commonly seen side effect of immunotherapy. Here we show that there is no significant correlation between grade of diarrhea and severity of colitis as seen during endoscopy. Chapters 4 and 5 describe patients with brain metastases and/or leptomeningeal metastases. In chapter 4 we show the difference in overall survival in patients treated with vemurafenib, dabrafenib or the combination of dabrafenib + trametinib. Chapter 5 focusses on the treatment of leptomeningeal metastases. Here a significant difference in overall survival was noted between treated and untreated patients. Furthermore LDH was a predictive biomarker for overall survival. In chapter 6 we show that treating patients with vemurafenib beyond progression of disease has a significant impact on overall survival. Lastly in chapter 7 we review the past, present and future of treating patients with different kinds of cancer with tumor-infiltrating lymphocytes.

• Melanoma
• Immunotherapy
• Targeted therapy
• Brain metastases
• Lepto meningeal metastases
• Colitis
• Biomarkers

• All authors: Geukes Foppen, M.H.
• Supervisor: Haanen, J.B.A.G.; Blank, C.U.
• Committee: Geluk, A.; Schumacher, T.N.M.; Gerritsen, W.R.; Gruijl, T.D. de; Brandsma, D.; Thienen, J.V. van
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2018-09-27
• ISBN (print): 9789493014534