Hyperprogression under immunotherapy: a new form of immunotherapy response?—a narrative literature review

Abstract

Objective: Update the last known review, and summarize the definitions, diagnostic criteria, reported risk factors, possible mechanisms and potential biomarkers of hyperprogressive disease (HPD) under immunotherapy.Background: Immunotherapy is a relatively new systemic therapy adding a new method of treatment of especially advanced cancer patients. In a variety of immunotherapies, however, an unexpected acceleration of tumor growth, known as HPD, is observed in approximately 30% of patients after immune checkpoint inhibitor (ICI) treatment. HPD has a deleterious survival effect on patients and represents an urgent issue for both clinicians and patients. Existing literature has reviewed and summarized the definition, diagnostic criteria, reported risk factors and possible mechanisms of hyperprogression. However, with the gradual deepening of the exploration of HPD, researchers have made significant breakthroughs in elucidating the mechanism and mechanism of HPD and exploring biomarkers. Methods:The search was conducted on Google Scholar and PubMed in January and May of 2021. We searched among English papers with no limitation on the publication year. We have included retrospective studies, case reports and basic researches related to HPD in the collection, we also referred to some review articles on HPD in recent years. A qualitative-interpretive approach was used for data extraction.Conclusions: HPD is considered to be an acceleration of tumor growth after ICI treatment that is not only due to immune infiltration but also due to real disease progression, with an incidence of about 4-30% in all retrospective published studies to date. Currently, the most widely used criteria of HPD contain Response Evaluation Criteria in Solid Tumors (RECIST) and tumor growth rate (TGR) or tumor growth kinetics.The common risk factors and underlying mechanisms of HPD have not yet been fully elucidated. However, based on the poor prognosis of HPD, there have been many advances in the exploration of biomarkers in recent years, like the prediction of HPD, such as LDH levels of peripheral blood, liquid biopsy, and radiomics, etc.

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis

“…The Economopoulou, Park, and Choi studies suggest younger age is a risk factor for HPD ( 38 , 44 , 48 ), whereas the studies published by Champiat, Hwang, and Refae point to elderly patients being disposed to suffer from HPD during or after immunotherapy ( 5 , 46 , 50 ). A potential mechanism is related to the ineffectiveness of intracellular antigens and the immune microenvironment in which immune cells and chemokines play a key role ( 77 ). As for the relationship between HPD and gender, the study by Kanjanapan was temporarily the only study reporting that women had a higher risk of HPD when receiving immunotherapy ( 58 ).…”

Correlation of preclinical and clinical biomarkers with efficacy and toxicity of cancer immunotherapy

“…It was reported that HPD is more likely to occur in patients with Royal Marsden Hospital score ⩾ 2, ECOG performance status ⩾ 2, more than two metastases, recurrent metastatic head and neck squamous cell carcinoma of the primary oral cavity, and PD-L1 positive combined score ⩾ 10 in liver metastasis of gastric cancer. 46 – 49 …”

From immune equilibrium to immunodynamics

“…At the same time, immunodynamic parameters can also be used to evaluate the severe adverse reactions caused by checkpoint inhibitors, including CRS. If the checkpoint blockade therapy induces an acute disequilibrium dominated by immune braking force, I predict that this response would lead to hyperprogression of disease (Champiat et al, 2018;Han et al, 2020;Lin et al, 2021). If this happens, treatment should be discontinued immediately and other therapies should be used depending on the situation.…”