The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Predictive serologic biomarkers are associated with immune checkpoint inhibitor-associated non-small cell lung cancer (NSCLC) hyperprogressive disease (HPD) in real-world settings, according to research conducted in South Korea and presented in a poster at the 2019 European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain.

If validated in additional research, the findings could lead to the development of clinical tools for identifying which patients face the greatest risk of developing HPD, which is characterized by extraordinarily accelerated tumor progression following immune-checkpoint inhibition. The findings might also prove useful in the study of the underlying molecular mechanisms of this condition, the authors reported.

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“Despite improved recognition of HPD, its etiology remains unclear, but it is clear that the prognosis becomes poor when it occurs,” reported coauthor Kim Joori of Seoul St Mary’s Hospital in Seoul, South Korea. 

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In a review of 243 patients who underwent immune checkpoint inhibition for NSCLC, the researchers found that 25 (10.8%) patients had experienced HPD. HPD was associated with worse overall survival (OS; 5.6 months vs 7.4 months; P <.001).

The study authors analyzed associations between HPD and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein–albumin ratio (CAR), and immune T-cell, macrophage, and natural killer (NK) cell markers, using multiplex immunohistochemistry (mIHC).

“Serologic markers at the time of first response evaluation (post 6 weeks) showed a prognostic value for HPD,” the authors reported (NLR, P <.001; PLR, P =.008; CAR, P =.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 [effector T] cells and FOXP3+ Treg [regulatory T] cells were associated with HPD (P <.042, P <.017, respectively).” 

CD4 to CD45RO ratio showed promising predictive utility for HPD (P < .042), they found.

The authors noted a tendency toward M2-state macrophage polarization in HPD. (Macrophage polarization is a response to cellular signals in the microenvironment.) That suggests that changes in the AXL tyrosine kinase membrane receptor pathway and epithelial-mesenchymal transition (EMT) might be involved in the emergence of HPD, the authors proposed.

“We observed that some serologic biomarkers and mIHC can be used not only to predict HPD, but also to validate its mechanism,” they concluded. 

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.


Kim J. Clinical implication of multiplex IHC and serologic biomarkers on hyperprogression in NSCLC patients receiving immune checkpoint blockers in real world. Presented at: European Society of Medical Oncology (ESMO) Congress 2019; Madrid, Spain: September 8-12, 2017. Abstract 1511P.