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Diagnostics (Basel). 2018 Oct 31;8(4). pii: E76. doi: 10.3390/diagnostics8040076.

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data.

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Molecular Health GmbH, 69115 Heidelberg, Germany.
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, 69120 Heidelberg, Germany.
Skin Cancer Unit, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, 69120 Heidelberg, Germany.


Recent studies suggest that combining nivolumab with ipilimumab is a more effective treatment for melanoma patients, compared to using ipilimumab or nivolumab alone. However, treatment with these immunotherapeutic agents is frequently associated with increased risk of toxicity, and (auto-) immune-related adverse events. The precise pathophysiologic mechanisms of these events are not yet clear, and evidence from clinical trials and translational studies remains limited. Our retrospective analysis of ~7700 metastatic melanoma patients treated with ipilimumab and/or nivolumab from the FDA Adverse Event Reporting System (FAERS) demonstrates that the identified immune-related reactions are specific to ipilimumab and/or nivolumab, and that when the two agents are administered together, their safety profile combines reactions from each drug alone. While more prospective studies are needed to characterize the safety of ipilimumab and nivolumab, the present work constitutes perhaps the first effort to examine the safety of these drugs and their combination based on computational evidence from real world post marketing data.


data mining; ipilimumab; melanoma; nivolumab; pharmacoepidemiology; proportional reporting ratio; real world data; side effects

Conflict of interest statement

T.G.S. is employee of Molecular Health GmbH and holder of patents related to the analysis of adverse event data.

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