Hyperprogressive disease with immunotherapy: new directions

Sally C. M. Lau, Natasha B. Leighl


The phenomenon of hyperprogression and its association with the use of immune checkpoint inhibitors (ICIs) has been increasingly described in recent literature. However, hyperprogressive disease (HPD) as a unique growth pattern remains controversial. HPD can be defined as the sudden acceleration of tumor growth kinetics above its baseline growth rate. The tumor genome is inherently unstable and changes affecting crucial mechanisms of cell growth can result in unexpeted changes in growth patterns. Small cell transformation in oncogene addicted cancers is an example of such sudden change. The point of contention with HPD is whether it is truly acceleration of growth caused by ICI exposure or simply a failure of antitumor efficacy (i.e., the tumor’s natural history). As ICIs move into the frontline treatment of several different cancer types, it is important to understand this phenomenon in order to avoid causing harm.