Clinical implication of multiplex IHC and serologic biomarkers on hyperprogression in NSCLC patients receiving immune checkpoint blockers in real world

Background Although immune checkpoint blockers (ICBs) can lead to favorable 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). Methods We reviewed NSCLC patients (n = 243) treated with ICBs. HPD was defined as a tumor growth kinetic ratio (TGKr)>2 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 immune compositional change in TME by multiplex IHC(mIHC). Panel 1/2 showed CD4, CD8, FOXP3, CD45RO as T cell markers and CD3, TIM3, LAG3, PD-L1 as co-inhibitory signal markers. Panel 3/4 examined macrophages and NK cells with CD68, CD14, CD163, CD206, CCR7, CD86, CD103, CD56, CD11c and CD16. Results Overall, 231 patients were evaluated. 25 patients (10.8%) met the HPD. Patients with HPD (median, 5.6 mo; P Conclusions Despite improved recognition of HPD, its etiology remains unclear, but it is clear that the prognosis becomes poor when it occurs. We observed that some serologic biomarkers (NLR, PLR, CAR) and mIHC can be used not only to predict HPD, but also to validate its mechanism. Furthermore, we undergo whole exon sequencing and experiment with murine model to understand mechanism of HPD. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.