Abstract 5004: A new pattern called Hyperprogression when using Immune checkpoint blockers in real world
Authors: Kim Seoree , Kim Sang-Yeob , Kang Jin Hyoung 
Published: August 2019

Abstract
Introduction Although immune checkpoint blockades (ICBs) therapy can lead to favorable and durable results by reinvigorating the anti-tumor immune response in some patients, many other patients experience poor prognosis and even tumor overgrowth can be seen in real practice. So, we performed retrospectively hyperprogression-related studies on patients who underwent immunotherapy to find the predictable clinical factor. We also revealed the difference of immune composition in TME that are associated with HPD by multiplex IHC
Method We retrospectively evaluated the medical records of NSCLC patients (n=243) who treated with anti-PD-1/anti-PD-L1 therapy at 5 institutes of St. Mary’s Hospitals between January 2014 to June 2018.
Results A total of 231 patients were included in the TGK analysis. Median age was 64.2 years with a majority being male (74.9%) and smokers (70.1%, n=162). Among them, 88.9% were heavy smokers with over 20 pack per years (n=144). Most of the ICB drugs were used in the second and above lines, but the proportion used in the fourth or higher heavy treated patients was 16%(n=37). The rate of over-growth was 33.3% (n=77) among these patients, the rate of hyperprogression was 32.4% (n=25). The proportion of patients harboring oncogenic driver mutation such as EGFR alteration was 18.6%. Univariate analyses indicated that HPD was significantly associated with oncogenic drive mutant status compared with non-HPD (18.6% [8 of 43] vs 9.04% [17 of 188]; P= 0.001). No significant differences were observed according to age, number of previous lines of therapy, or presence of more than 3 metastatic sites before ICBs. Multivariate analyses with a multivariate logistic regression model demonstrated that presence of less than 3 metastatic sites (odds ratio [OR], 4.769; 95% [CI], 1.384-16.433; P &lt; .013) was an independent predictor for HPD. We also analyzed the association of NLR, PLR and CAR with HPD. Serologic markers post 6 weeks, i.e., at the time of first response evaluation, showed prognostic value for the most significant hyperprogression after ICB use. Kaplan-Meier OS estimates showed that there was a clear trend toward worse outcome for the patients with HPD (median OS, 5.6 months;95% CI, 4.5-10.3; P &lt; 0.001) compared with the patients with non-HPD disease progression (median OS, 7.4 months; 95% CI, 15.1-19.6; P = 0.003) The multiplex IHC results showed that the percentage of T-cell marker expression of Tumor and Stroma in each slide was different between good responder and HPD.
Conclusion Even though the improved recognition of hyperprogression, the etiology of HPD remains unclear, apart from the pseudoprogression. However, we observed that some clinical factors and some serologic biomarker can be used to predict HPD. Furthermore, we undergo TMB and multiplex IHC to understand mechanism of hyperprogression.
Citation Format: Seoree Kim, Sang-Yeob Kim, Jin Hyoung Kang. A new pattern called Hyperprogression when using Immune checkpoint blockers in real world [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5004.