Clinical implication of inflammation-based serologic biomarkers and tissue biomarkers on hyperprogression in NSCLC patients receiving immune checkpoint blockers in real world.

Abstract

e20633 Background: 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. We aimed to assess these hyperprogressive disease (HPD) in patients who underwent ICB therapy. Methods: We retrospectively reviewed medical records of non-small cell lung cancer patients (n = 243) treated with anti-PD-1 or anti-PD-L1 monotherapy. HPD was defined as a tumor growth kinetics ratio > 2 during anti-PD-1/PD-L1 therapy and a time-to-failure of less than 2 months. We analyzed the association of Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and CRP-albumin ratio (CAR) with HPD and the difference of immune composition in TME by multiplex IHC. Results: Overall, 231 patients were included. The median age was 64.2 years; most patients were male (74.9%) and smokers (70.1%, n = 162). 25 patients (10.8%) met the criteria for HPD. Oncogenic drive mutant status was significantly associated with HPD (18.6% vs 9.04%; P = 0.001). Kaplan Meier overall survival estimates showed a clear trend toward worse outcomes for patients with HPD (median, 5.6 months; P < 0.001) than for those without (median, 7.4 months). We also analyzed the association of NLR, PLR and CAR with HPD. Serologic markers at the time of first response evaluation (post 6 weeks, i.e.,) showed a prognostic value for HPD after ICB use ( P < 0.001, 0.008, 0.017). In multiplex IHC, there was no difference in T cell related immune marker of CD 3/4/8/45RO and FOXP3, dendritic cell, NK cell and other co-inhibitory signal markers between two groups. However, the key point was the M2 polarized tendency in the HPD group when the macrophage M1 / 2 markers of CD68, CD163, CD206 and CCR7 were observed. This suggests that changes in the AXL pathway and EMT features associated with reinvigorating anti-tumor immunity in M2 polarized cells may lead to changes in poor prognosis to HPD. Conclusions: Despite improved recognition of HPD, its etiology and predisposing factors remain unclear, but it is clear that the prognosis becomes poor when it occurs. We observed that some serologic biomarkers (NLR, PLR and CAR. i.e.,) can be used to predict HPD. Multiplex IHC can be used not only to predict HPD, but also to validate its mechanism. Furthermore, we undergo whole exon sequencing and multiplex IHC to understand mechanism of Hyperprogression.