3659 - 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 < 0.001) were worse outcome than those for without (median, 7.4 mo). 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 (P < 0.001, 0.008, 0.017). In mIHC, there was a difference in immune cell composition between the HPD, poor responder and good responder groups. High levels of CD4+ Teff cells and FOXP3+ Treg cells were associated with HPD (p < 0.042, <0.017) The CD4 to CD45RO ratio suggests a predictive ability to develop HPD (p < 0.042) The key point was the M2 polarized tendency in the HPD group. This suggests that changes in the AXL pathway and EMT features associated with reinvigorating anti-tumor immunity in M2 polarized cells may lead to HPD.

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.