Nivolumab serum concentration in metastatic melanoma patients could be related to outcome and enhanced immune activity: a gene profiling retrospective analysis. Issue 11 (24th November 2022)

• Record Type: Journal Article
• Authors: Mallardo, Domenico; Giannarelli, Diana; Vitale, Maria Grazia; Galati, Domenico; Trillò, Giusy; Esposito, Assunta; Isgrò, Maria Antonietta; D'Angelo, Grazia; Festino, Lucia; Vanella, Vito; Trojaniello, Claudia; White, Andrew; De Cristofaro, Teresa; Bailey, Michael; Pignata, Sandro; Caracò, Corrado; Petrillo, Antonella; Muto, Paolo; Maiolino, Piera; Budillon, Alfredo; Warren, Sarah; Cavalcanti, Ernesta; Ascierto, Paolo Antonio
• Is Part Of: Journal for immunotherapy of cancer. Volume 10:Issue 11(2022)
• Publication Date: 2022-11-24
• Subjects: Melanoma -- Immunotherapy -- Tumor Biomarkers; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2022-005132
• Languages: English
• ISSNs: 2051-1426

Abstract

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.