1131P C-reactive protein as biomarker for immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors in the adjuvant setting

Abstract

Background: Inherited pathogenic variants (PV) in the CDKN2A tumour suppressor gene are among the strongest known risk factors for cutaneous melanoma. CDKN2A encodes for the cell cycle inhibitors p16 ink4 and p14ARF, and dysregulation of the p16/RB1 pathway is a well-known mechanism of resistance to MAPK-directed targeted therapy due to the interplay between the two pathways. For this reason, we wondered whether patients with germline CDKN2A PVs may achieve suboptimal results with BRAF and MEK inhibitors.Methods: We identified twenty CDKN2A PVs carriers who received first-line treatment with BRAF and MEK inhibitors for BRAF-mutant advanced melanoma by reviewing medical records of carriers enrolled in follow-up studies for familial melanoma. By a binomial test, we evaluated if there was a statistically significant difference in the response rate observed in the carriers compared with an expected rate calculated from phase III clinical trials and "real-world" studies. Results:The baseline prognostic features of the 20 identified patients were poorer than those reported in phase III clinical trials, with 12 patients (60%) having stage M1c disease and 5 patients (25%) brain metastases at baseline. Seventeen patients (85%) achieved a partial response; no complete responses were observed. The overall response rate was numerically higher than that expected from phase III trials (66%), although not statistically significant (p-value¼0.097; 95% CI: 0.62-0.97); the difference was statistically significant (p-value¼0.012; 95% CI: 0.62-0.97) when the comparison was performed with real-world studies. Conclusions:The clinical activity of BRAF and MEK inhibitors in patients with BRAFmutant advanced melanoma and germline CDKN2A PVs was not inferior to that observed in clinical trials and real-world studies, which we believe is helpful information for clinicians who manage patients with melanoma.Legal entity responsible for the study: The authors.

Common statement of experts of the Polish Oncological Society, Polish Lung Cancer Group, Polish Society of Lung Diseases, Polish Society of Gastroenterology, Polish Society of Endocrinology, and the Polish Society of Cardiology for minimal requirements in diagnosis and monitoring of selected adverse events of immunotherapy in oncological patients

“…Laboratory analyses are helpful in differential diagnosis of other coexisting organ toxicities of immunotherapy. Immunological pneumonitis is associated with a moderate increase in C-reactive protein (CRP) concentration, and a decrease in CRP concentration correlates with response to treatment [25]. Therefore, additional laboratory tests (e.g., determining procalcitonin concentrations in serum) or bacteriological and virological analyses may be necessary to differentiate IP and pneumonia caused by an infectious agent.…”

Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications

“…Another very interesting field of research is the investigation of predictive markers in terms of drug-related adverse events. In a recent study, Lauwyck and colleagues [ 59 ] found how C-reactive protein (CRP) may be of use in predicting immune-related adverse events (irAE) related to adjuvant treatment with immune checkpoint inhibitors. Through retrospective analysis of 72 melanoma patients, they observed how in patients that experience irAE, the median serum CRP-levels exceeded the ULN (5 mg/L).…”