Predicting the likelihood of elevated transaminases in lung cancer patients undergoing immune checkpoint blockade

Background The recent implementation of immune-checkpoint inhibitors (ICIs) has markedly changed the management and clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC). Despite higher efficacy, ICIs are associated with a range of immune-related adverse events (irAEs). This retrospective study aimed to investigate the incidence of ICI-related transaminitis/hepatitis in NSCLC patients as well as to establish if any pre-treatment clinical parameters can predict the onset of liver toxicity. Methods We examined medical records of N=420 NSCLC patients treated across two health districts in Sydney, Australia between 2016 to 2020. R packages (corrplot and ggcorrplot) were used to construct correlation matrices and to calculate the correlation p-value using Spearman method. Logistic regression models were used to determine association of clinical parameters with elevated LFTs. Results N=185 patients were considered eligible. n=37 (20%) had elevation of liver transaminases at any stage post-ICI commencement, although only n=10 were deemed as those having ICI-related hepatitis. Most of these patients (n=29 [78%]) developed elevated LFTs within 3 months post-therapy initiation. Regression model established that pre-treatment ratio of serum protein (SP) to total bilirubin (TB) showed significant association with the elevated transaminases. Moreover, most of the patients (n=34 [94%]) with elevated LFTs had SP/TB<4. Using a second cohort of melanoma patients, the linear regression model did not establish a significant association between the SP/TB ratio and elevated LFTs. Nonetheless, n=31 (70.5%) patients with immune-mediated transaminitis in the melanoma cohort had SP/TB<4. Conclusion Our study has established a clinical risk factor associated with the elevation of LFTs in NSCLC patients, thus potentially enabling their prediction at the pre-treatment stage. However, its predictive accuracy was not confirmed in melanoma patients, stressing that ‘ one size does not fit it all ’ when developing predictive scores for irAEs in different patient cohorts.