Immune checkpoint inhibitor (ICI) has now become the new standard treatment for non-small-cell lung cancer (NSCLC). Immune-related adverse events (irAEs) are frequently observed. Little is known about the predictor of the development of irAEs in NSCLC patients.
Patients with advanced NSCLC treated with nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 137) between January 2016 to January 2018 were included in our study. Subjects were divided into either each pre-existing antibody group or non-pre-existing antibody group, and we analyzed the association with clinical benefit and irAEs. They were also further categorized into either the irAEs-incident group (irAEs group) or non-irAEs-incident group (Non-irAEs group) and we analyzed available predictive factors of development of irAEs in clinical setting. Antibody were drawn at screening to measure immune safety parameters (anti-thyroglobulin antibody, anti-thyroid peroxidase antibody, rheumatoid factor (RF), and antinuclear antibody (ANA)).
Categorization of irAEs identified 14 of interstitial pneumonia (10%), 42 of skin reactions (31%), 16 of thyroid dysfunction (12%), and 6 of hepatitis (4%), 5 of myositis/peripheral neuropathy (4%). The following were observed: patient background (irAEs/Non-irAEs group) number of cases 66/71 cases, median age 68/67 years old, male 82/72%, treatment response CR/PR/SD/PD (1/37/27/5)/(1/8/26/36), ORR 52% (34 cases)/13% (9 cases) [Odds ratio: 0.137, p <.001]. Univariate analysis identified a significantly more pre-positivity RF in the irAEs group than in the non-irAEs group. Upon multivariate analysis, the pre-existing of RF [Odds ratio: 0.30, p = 0.003] and the pre-existing of ANA [Odds ratio: 0.47, p = 0.028] were identified as independent predictors of development of irAEs. Median PFS (months) of pre-existing RF group was significantly longer than that of non-pre-existing RF group [10.1/3.7 months, respectively, HR (95% CI) 0.61 (0.38–0.97), p = 0.036].
The pre-existing of RF for NSCLC were independent predictors of development of irAEs and might be associated with improved outcomes.
Clinical trial identification
Legal entity responsible for the study
Sendai Kousei Hospital.
Has not received any funding.
S. Sugawara: Ono Pharmaceutical Co, Bristol-Myers Squibb, MSD. All other authors have declared no conflicts of interest.