Molecular And Clinical Features Of Hospital Admissions And Immunotherapy Related Adverse Events Of Immune Checkpoint Inhibitors In Thoracic Malignancies.

JOURNAL OF CLINICAL ONCOLOGY(2019)

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摘要
e18192 Background: Immunotherapy related adverse events (irAEs) and hospital admissions with Immune Checkpoint Inhibitors (ICIs) in thoracic malignancies remain poorly characterized. Methods: Admissions after ICIs in all thoracic malignancies patients received ICIs at City of Hope (total 384) were identified as of 11/8/2018. IrAEs, outcomes, pathology and next-generation sequencing (NGS) data were collected, including Tumor mutation burden (TMB) and PD-L1 (22C3). Length of stay (LOS) and overall survival (OS) was calculated. Unpaired T-tests if data passed normality test, Chi-square and Fisher’s exact test, Gehan-Breslow-Wilcoxon test were used for comparison between 2 groups (irAEs VS no irAEs) for LOS, demographics and genetics, and survival respectively. Results: 100 patients had hospital admissions after ICIs therapy and 90 patients (41 women, 49 men) had stage IV disease (63 lung adenocarcinomas, 14 squamous cell lung cancer, 5 small cell lung cancer, 8 others). 28 out of 90 patients had irAEs (10 pneumonitis/pneumonia, 4 adrenal insufficiencies, 4 colitis, 3 liver toxicities, 2 nephritis, 1 heart failure, 1 pancreatitis, 1 diabetic ketone acidosis, and others including multiple irAEs). There was no difference between the patients who had irAEs VS no irAEs in LOS (median 7 days VS 6 days, P = 0.57). Patients with irAEs had more invasive diagnostic procedures than no irAEs (53.6% VS 25.8%, P = 0.02). There was a trend of longer OS in irAEs patients (median 16.4 months VS 6.8 months, P = 0.13) than no irAEs. Male gender (71.4% (20/28) VS 46.8% (29/62), OR = 2.85, P = 0.04) and smoking exposure (89.3% (25/28) VS 58.1% (36/62), OR = 6.0, P < 0.01) were associated with irAEs patients. Genetic alterations of LRP1B gene (83.3% (5/6) VS 26.9% (7/26), OR = 13.6, P = 0.02) and MLL3 gene (66.7% (4/6) VS 19.2% (5/26), OR = 8.4, P = 0.04) were associated with patients who had irAES. No difference was found in age, lines of therapy, TP53, KRAS, EGFR, STK11, PIK3CA, TMB, PD-L1 between the irAEs and no irAEs patients. Conclusions: Hospitalized patients who had irAEs had similar LOS compared with patients without irAEs but potentially longer OS. Gender, smoking status and genes associated with irAEs and ICIs outcomes were explored. Larger dataset for molecular and clinical features was planned.
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