Outcome and treatment-related adverse events of combined immune checkpoint inhibition with flipped dosing in a real-world cohort of 79 patients with metastasized melanoma.

Combined immune checkpoint inhibition (ICI) with ipilimumab and nivolumab is a widely used treatment regimen for metastatic melanoma with non-resectable metastases. Nevertheless, the standard dose of ipilimumab 3 mg/kg bw and nivolumab 1 mg/kg bw is associated with a high rate of treatment-related adverse events (trAEs) (59% grade 3-4). In the CheckMate 511 study, it could be shown that flipped dosing with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw resulted in a significant reduction of trAE. We have also used this regimen in the clinical setting and report the trAE, progression-free survival, and overall survival for 79 patients with metastatic melanoma who started combined ICI in the flipped dosing between March 2019 and April 2020. in total, 40 patients started first-line, 50% of whom had an elevated lactate dehydrogenase level at baseline. The disease control rate of these patients was 50%. The 2-year overall survival rate 67%. Moreover, 33% of the patients suffered grade 3 or 4 treatment related adverse events. The results of our study correspond very well to the results of the CheckMate 511 study (2-year OS: 65%, grade 3-4 immune-related side effects: 35%). Combined ICI with ipilimumab 1 mg/kg bw and nivolumab 3 mg/kg bw seems to be an equally effective but better-tolerated therapy regimen for metastasized melanoma patients, also in a real-world cohort.

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Copyright © 2023 Nübel, Amaral, Leiter, Flatz and Forschner.

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TA reports institutional funding from SkylineDx B.V. in relation to the submitted work. TA reports personal honoraria from BMS, CeCaVa, Novartis and Pierre-Fabre; Institutional financial support from iFIT, Neracare, Novartis and Sanofi and institutional research Grant from Novartis, outside the submitted work. UL reports research support from MSD, consulting fees and honoraria from Sun Pharma, Sanofi personal and institutional, MSD personal and institutional, Novartis, Roche, Almirall Hermal, support for attending meeting from Sun Pharma and participation on a Data Safety Monitoring Board or Advisory Board from Sun Pharma, Sanofi, MSD, Novartis, Roche, Almirall Hermal, outside the submitted work. LF reports Grants or contracts from Hookipa Pharma, SAKK/Immunophotonics, DFG Grant Deutsche Forschungsgemeinschaft, Philogen and Mundipharma; consulting fees from Philogen, Sanofi, Novartis, BMS; participation on Data Safety Board University of Basel and stocks or stock options from Hookipa Pharma, outside the submitted work. AF reports honoraria for presentations for BMS, MSD, Novartis, Pierre-Fabre; Travel support and congress participation support from BMS, Pierre-Fabre, Novartis; Advisory Boards from MSD, BMS, Novartis, Pierre-Fabre, Immunocore and institutional funding from BMS Stiftung Immunonkologie, outside the submitted work. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.