Identifying blood bio-markers for immunotherapy toxicity in melanoma patients


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Anna Olsson-Brown1,Charlotte Hogg1,Marie Allirajah1,Joseph Hanna1,Tsz Hin Lo1,Anusha Yoganathan1,Umair Akbani1,Helen Wong2,Marie McKay3,Shien Chow3,Joseph Sacco2
1University of Liverpool,2University of liverpool,3Clatterbridge Cancer Centre

Abstract

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the management of metastatic melanoma, however immune related adverse events (irAEs) are common and unpredictable. Routinely used blood markers, such as neutrophil and lymphocyte counts, have been shown to correlate with efficacy outcomes. There has however been little study of their potential in predicting toxicity.

Method

A single centre retrospective study of patients with metastatic melanoma who commenced ICIs between 2016 and 2018 was undertaken. Data were collected by 5 medical students during their research module. Blood results from baseline, cycles 2-5 and 6, 9 and 12 months after commencing ICIs were extracted from the electronic medical records (Meditech) and correlated with irAEs (type, onset, severity). Analysed parameters included haemoglobin, lymphocytes, neutrophils, eosinophils, platelets, sodium, phosphate, C-reactive protein(CRP), albumin and calcium. Analysis was performed in SPSS.

Results

154 patients were included in the study. The overall incidence of toxicity was 67.5%; 56.4% (monotherapy pembrolizumab) and 86.5% (combination ipilimumab and nivolumab). With regard to toxicity, statistically significant differences in the baseline, and/or second cycle levels of several parameters, including albumin, phosphate, neutrophils and eosinophils, were observed. Early elevation in eosinophils (p=0.027) and albumin (p=0.022)were associated with pan-toxicity. Elevated baseline albumin or eosinophil count were associated with colitis and pneumonitis respectively. In combination ICI therapy higher baseline neutrophils were associated with toxicity (p=0.001). A progressive difference in lymphocytes delineated between those with/without toxicity with higher levels of lymphocytes associated with irAEs. Differences in platelet count, CRP and calcium were not associated with irAEs.

Conclusion

Our study demonstrates that several routinely assayed blood markers correlate with the incidence of irAEs, and may ultimately be used in a composite score to predict irAE risk. We are currently validating our findings in a second cohort of melanoma patients and a renal cohort; however prospective validation will ultimately be required.