Immune checkpoint inhibitors (ICIs) have changed the treatment of pts with aNSCLC and mMel. No predictive markers of development of irAEs are available. Aim of the study is to evaluate the role of circulating markers in predicting irAE onset.
We reviewed clinical data of aNSCLC and mMel pts treated with ICIs at Istituto Oncologico Veneto (Padova, Italy) and San Bortolo Hospital (Vicenza, Italy) between January 2012 and January 2019. We collected data on type and grading (G) of irAEs and calculated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) before first ICI administration and at irAE onset. Values were dichotomized in: high (H) and low (L) NLR and H- and L-PLR, using pre-identified cut-offs of 3 and 180 for aNSCLC, 3 and 120 for mMel.
Analysis included 377 pts (252 aNSCLC and 125 mMel). In aNSCLC cohort, median PFS and OS were 4.9 months (m) (95% CI: 3.6-6.1) and 8.6m (95% CI: 6.3-10.8). Ninety-seven pts (38%) developed irAEs, mainly G1-2 (72%), with permanent ICI discontinuation in 29 (29.9%) cases; 26 pts (26.8%) experienced more than one irAE. Pts with baseline L-NLR or L-PLR had a higher risk of irAE (OR = 2.3, 95% CI: 1.3-3.9, p = 0.002 | OR = 2.4, 95% CI: 1.3-4.1, p = 0.02). Multivariate analysis confirmed NLR and PLR as independent predictive markers (OR = 1.8, 95%CI: 1.0-3.2, p = 0.04 | OR = 1.9, 95%CI: 1.0-3.4, p = 0.03). L-PLR at irAE onset was associated with risk of irAE recurrence or second irAE development (OR = 4.2, 95% CI: 1.4-12.9, p = 0.01). In mMel pts, median PFS and OS were 5.1m (95% CI: 3.6-6.5) and 18.1m (95% CI: 11-25.2). Fifty-four pts (43%) developed irAEs, mainly G1-2 (76%), with permanent ICI discontinuation in 10 (18.5%) cases; 14 pts (25.9%) had multiple irAEs. Pts with baseline L-NLR had higher risk of irAE (OR = 2.2, 95% CI: 1.1-4.6, p = 0.04). NLR and PLR at time of irAE onset were not associated with the risk of irAE recurrence or second irAE development.
Baseline NLR and PLR may be reliable and inexpensive predictive tools of irAE risk. For aNSCLC pts L-PLR at irAE onset correlates with risk of further toxicity. If validated, these biomarkers may help pts’ management during ICIs and treatment handling after a first irAE.
IRCCS Istituto Oncologico Veneto - IOV - Padua – Italy.
Has not received any funding.
All authors have declared no conflicts of interest.