Abstract
95 Background: Identifying patients who will benefit from immune-checkpoint inhibitor therapy is a challenge as proven predicative indicators remain to be elucidated. High tumor mutational burden (TMB) represents a possible biomarker for response to PD1 blockade such as in nivolumab or pembrolizumab. Genomic analyses have shown that patients with heavy smoking history are more likely to have high TMB. However smoking status alone has not been examined independently in relation to treatment response. We sought to determine whether a relationship existed between smoking history and response to treatment in metastatic non-small cell lung cancer (NSCLC), metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mMelanoma). Methods: A retrospective analysis was conducted of Ochsner Health System patients with mRCC, mMelanoma, and NSCLC receiving a minimum of two cycles of nivolumab or pembrolizumab between 12/2014 and 01/2018. Pre- and post-treatment target lesions were analyzed using RECIST criteria to calculate best response to treatment. Patient demographic information was gathered including age, sex, smoking history, and performance status pre and post treatment. Kaplan-Meier method was used to estimate progression free survival (PFS) and overall survival (OS) outcomes. Results: Heavy smokers (>10 pack-years) had a higher response to immunotherapy than light (< 10 years) and never smokers (p = 0.0500). Heavy smokers with NSCLC treated with immuno-therapy also had significantly improved OS compared to light smokers with NSCLC (p=0.003). mRCC immuno-therapy patients with heavy smoking history showed increased PFS compared to light/never smokers (p=0.026). Conclusions: In summary, in response to PD-1 blockade heavy smokers showed improved survival compared to light and never smokers suggesting smoking history may represent a potential predictor of treatment response to PD-1 inhibitor therapy.[Table: see text]
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