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Observational Study
. 2022 Nov;10(11):e005132.
doi: 10.1136/jitc-2022-005132.

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis

Domenico Mallardo  1 , Diana Giannarelli  1 , Maria Grazia Vitale  1 , Domenico Galati  1 , Giusy Trillò  1 , Assunta Esposito  1 , Maria Antonietta Isgrò  1 , Grazia D'Angelo  1 , Lucia Festino  1 , Vito Vanella  1 , Claudia Trojaniello  1 , Andrew White  2 , Teresa De Cristofaro  1 , Michael Bailey  2 , Sandro Pignata  1 , Corrado Caracò  1 , Antonella Petrillo  1 , Paolo Muto  1 , Piera Maiolino  1 , Alfredo Budillon  1 , Sarah Warren  2 , Ernesta Cavalcanti  1 , Paolo Antonio Ascierto  3
Affiliations
Observational Study

Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis

Domenico Mallardo et al. J Immunother Cancer. 2022 Nov.

Erratum in

Abstract

Background: Nivolumab is an anti-PD-1 antibody approved for treating metastatic melanoma (MM), for which still limited evidence is available on the correlation between drug exposure and patient outcomes.

Methods: In this observational retrospective study, we assessed whether nivolumab concentration is associated with treatment response in 88 patients with MM and if the patient's genetic profile plays a role in this association.

Results: We observed a statistically significant correlation between nivolumab serum concentration and clinical outcomes, measured as overall and progression-free survival. Moreover, patients who achieved a clinical or partial response tended to have higher levels of nivolumab than those who reached stable disease or had disease progression. However, the difference was not statistically significant. In particular, patients who reached a clinical response had a significantly higher concentration of nivolumab and presented a distinct genetic signature, with more marked activation of ICOS and other genes involved in effector T-cells mediated proinflammatory pathways.

Conclusions: In conclusion, these preliminary results show that 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.

Keywords: Immunotherapy; Melanoma; Tumor Biomarkers.

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Conflict of interest statement

Competing interests: PAA has/had a consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Italfarmaco, Nektar, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, Seagen, iTeos, Medicenna, Bio-Al Health. He also received research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi. SW is employee and stockholder in NanoString Technologies. All other authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Relationship between nivolumab serum concentration and overall survival (A) or progression free survival (B).
Figure 2
Figure 2
Gene expression analysis of patients who reached a complete response versus other patients. The triangle shape indicate the following genes: protumor genes (red), immune suppressor pathway (gray), apoptosis pathway (yellow), antitumor genes (green), immune activation pathway (blue) and genes related with drug concentration (black). Genes marked with asterisk are related to drug concentration.
Figure 3
Figure 3
Flow cytometry analysis.
See this image and copyright information in PMC

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