Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhance immune activity: a gene profiling retrospective analysis
Authors/Creators
- Domenico Mallardo1
- Diana Giannarelli2
- Domenico Galati1
- Maria Grazia Vitale1
- Giusy Trillò1
- Assunta Esposito1
- Maria Antonietta Isgrò1
- Grazia D'Angelo1
- Lucia Festino1
- Vito Vanella1
- Claudia Trojaniello1
- Alessandro Manzoni1
- Andrew White3
- Teresa De Cristofaro1
- Michael Bailey3
- Sandro Pignata1
- Corrado Caracò1
- Antonella Petrillo1
- Paolo Muto1
- Piera Maiolino1
- Alfredo Budillon1
- Sarah Warren3
- Ernesta Cavalcanti1
- Paolo Antonio Ascierto1
- 1. Istituto Nazionale Tumori - IRCCS - Fondazione "G. Pascale", Naples, Italy
- 2. Regina Elena National Cancer Institute, IRCCS, Roma, Lazio, Italy
- 3. NanoString Technologies, Seattle, USA
Description
Nivolumab is an anti-PD1 antibody approved for the treatment of metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient’s outcomes. In this observational retrospective study we assessed whether nivolumab concentration is associated with treatment response in patients with MM, and if patient’s genetic profile plays a role in this association. We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall survival and progression free survival. Moreover, patients who reached a clinical response (CR) had significantly higher concentration of nivolumab and presented a distinct genetic signature, with a more marked activation of ICOS and other genes involved in effector T-cells mediated pro-inflammatory pathways.
In conclusion, in patients with MM nivolumab concentration correlates with clinical outcomes and is associated with an increased expression of ICOS and other genes involved in the activation of T effectors cells.
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