Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review

The emergence of immune checkpoint inhibitors (ICIs) has ushered in a new era of tumor immunotherapy. These agents function by specifically binding to immune checkpoints, blocking the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway, and inhibiting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) signaling. This action suppresses the negative immune regulatory mechanisms of tumors, prevents immune escape, and activates T cells. Consequently, ICI treatment restores the cytotoxic activity of effector T cells against tumor cells, exerts antitumor effects, delays tumor progression, and ultimately prolongs patient survival while improving clinical outcomes. ICIs have now been approved for first-line or second-line treatment of various malignancies. However, in some patients, immunotherapy not only fails to confer a survival benefit but may also lead to rapid tumor progression shortly after treatment initiation, a phenomenon clinically known as hyperprogressive disease (HPD). Currently, research on the underlying mechanisms, predictive biomarkers, and effective therapeutic strategies for HPD remains limited. This article comprehensively reviews the definition, differential diagnosis, pathogenesis, and potential predictive markers of HPD, including inflammatory and immune-related biomarkers, clinical factors, and tumor-related markers. The objective of this study is to provide a theoretical foundation and practical guidance for the early identification of HPD and the optimization of clinical treatment strategies.