Hyperprogressive disease under anti-PD-1 rechallenge after initial response to anti-PD-1 treatment for non-small cell lung cancer: a case report

Abstract

Background: Hyperprogressive disease is an unexpected response pattern observed in immune checkpoint therapy and associated with poor prognosis. The rechallenge of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors can be a treatment option in non-small cell lung cancer (NSCLC) patients who once responded to them. Here, we reported the hyperprogressive phenomenon after PD-1/PD-L1 rechallenge in a patient with NSCLC.

Case description: This case report described a patient with recurrent large cell lung cancer undergoing hyperprogressive disease with pleural and pericardial dissemination shortly after the pembrolizumab rechallenge, although he had a favorable response to the initial pembrolizumab treatment. A lower ratio of CD8⁺ T cells to Foxp3⁺ regulatory T cells was distributed in the cell blocks of pleural and pericardial effusion which were taken after hyperprogressive disease, compared to the resected tumor microenvironment. Neutrophil-to-lymphocyte ratio (NLR) was lower in peripheral blood when the disease was controlled and it rose when the disease progressed. Notably, NLR increased dramatically when hyperprogression occurred.

Conclusions: For the first time, we reported that a patient who showed a favorable response to initial anti-PD-1 treatment underwent hyperprogressive disease when rechallenging the same immunotherapy. The increased Foxp3⁺ regulatory T cells in the tumor microenvironment and the longitudinal change of NLRs in peripheral blood were suggested to be associated with hyperprogressive disease.

Keywords: Foxp3+ regulatory T cells; Non-small cell lung cancer (NSCLC); anti-programmed cell death 1 rechallenge (anti-PD-1 rechallenge); case report; hyperprogressive disease.