Hyperprogression of brain metastases following initiation of immune checkpoint inhibitors

Purpose: Immune checkpoint inhibitors (ICI) are increasingly being administered to cancer patients, including those with brain metastases (BMs). However, in a subset of cancer patients, ICI have shown to paradoxically accelerate tumor growth. This phenomenon is known as hyperprogressive disease (HPD). The aim of this study is to investigate the occurrence of HPD following initiation of ICI in BM patients. Methods: We retrospectively reviewed the charts of 60 surgically treated patients with BMs from non-small cell lung cancer or melanoma who were administered ICI at the Brigham and Women's Hospital, Boston between July 2008 and July 2018. BM tumor volumes before and after initiation of ICI were collected. HPD was defined as a 'post-immunotherapy' tumor growth rate (TGR) > 2 times 'pre-immunotherapy' TGR within three months following initiation of ICI. Results: Among the 25 included patients treated with ICI, five patients showed HPD with an increase of post-immunotherapy TGR ranging from 4.9 to 207.7 times the pre-immunotherapy TGR. The median survival after initiation of ICI was was 8.0 months in the HPD cases and 13 months in the non-HPD patients. Conclusion: HPD occurred in about 20% of BM patients receiving ICI. More research is necessary to prospectively analyze the occurrence of HPD and identify predictive factors for HPD in BM patients.