Background Immune-related adverse events (irAEs) are a unique characteristic of immune checkpoint inhibitors (ICIs) and can confer survival benefits. For example, melanoma patients who develop vitiligo as an irAE tend to have improved overall survival (OS), hypothesized to be due to molecular mimicry between similar antigens.^{1 2} Further analysis of the impact of irAEs on OS among real-world lung cancer patients is needed; this study addresses this need in a hospitalized population.^3–5

Methods This single-center retrospective cohort study collected data on a subset of lung cancer patients who received > 1 dose of an ICI (nivolumab or pembrolizumab) between 6/1/18 and 2/1/20 (n=210) and who were subsequently hospitalized and received > 1 dose of systemic corticosteroids for any indication (n=97). Patients were stratified according to whether or not they developed irAEs at any point. Clinical factors for data collection included: comorbidities, irAE development (organ and grade), cancer stage, ICI cycles, biomarkers, progression, and survival. OS analysis was calculated from the first dose of ICI to date of death or last known follow-up. To assess significance, the log-rank approximation of the chi-square test was used.

Results Kaplan-Meier survival analysis revealed that patients who developed irAEs (n=28, median OS 14.9 months) did not have an association with increased median OS when compared to patients without irAEs (n=69, 8.7 months, p 0.072) (table 1). The subgroup of patients who developed either colitis or pneumonitis had an increased median OS (n=15, 41.3 months, p 0.049) compared to patients without irAEs . Patients who only experienced grade ≥ 3 irAEs (n = 20, median OS 17.0 months, p 0.095) did not show any OS difference compared to patients without irAEs. Patients who developed ≥2 irAEs of any grade (n = 7, median OS 17.0 months, p 0.22) did not show any OS difference as compared to patients without irAEs.

Conclusions Initial analysis shows that while generalized irAEs in this hospitalized lung cancer population were not significantly associated with OS change, patients who developed pneumonitis and colitis were associated with treatment response and increased OS. Patients could be developing an interaction between pneumonitis and lung cancer analogous to the interaction between vitiligo and melanoma via molecular mimicry, resulting in improved OS. Thus, certain organ-related irAEs may indicate an immune response to ICIs depending on the malignancy being treated, correlating with improved prognosis.

References

1. Bertrand A, Kostine M, Barnetche T, Truchetet M-E, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med 2015;13:211.

2. Teulings H-E, Limpens J, Jansen SN, et al. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. J Clin Oncol 2015;33(7):773–81.

3. Owen DH, Wei L, Villalona-Calero MA, et al. Impact of immune-related adverse events (irAE) on overall survival (OS) in patients treated with immunotherapy for non-small cell lung cancer (NSCLC). J Clin Orthod 2017;35(15_suppl):9080–9080.

4. Haratani K, Hayashi H, Chiba Y, et al. Association of immune-related adverse events with nivolumab efficacy in non–small-cell lung cancer. JAMA Oncol 2018;4(3):374–8.

5. Owen DH, Wei L, Bertino EM, et al. Incidence, risk factors, and effect on survival of immune-related adverse events in patients with non–small-cell lung cancer. Clin Lung Cancer 2018;19(6):e893–900.

Ethics Approval The study protocol was approved by Wake Forest Baptist Medical Center's institutional review board.