Hyperprogression in cancer patients on immunotherapeutic agents.

Abstract

3575 Background: Patients (pts) treated with checkpoint inhibitors (CPI) may uncommonly experience accelerated progression in their tumor burden when compared to their rate of progression prior to receiving CPI. This hyperprogression has been varyingly defined and no biomarker has yet been identified. Methods: We reviewed the database from the Tumor Response Assessment Core (TRAC) at University of Michigan to identify these patients. Hyperprogression was defined as increase in tumor burden per specific immune RECIST criteria by at least 40% from baseline on the first follow-up scan with a minimum increase of 10 mm, and at least 2 times rate of growth than observed prior to start of CPI therapy. Results: Out of 741 pts who underwent baseline and 1st follow-up assessment enrolled on 118 trials, 302 (34.4%) pts received immunotherapy alone or in combination with chemotherapy/targeted agents across 49 trials. Of them, 15 pts (5%) with 5 females (33%) and median age of 63 years (range, 44 -72) met criteria for hyperprogression. The primary cancers included lung (5), colorectal (2), renal (2), biliary (1), pancreatic (1), esophageal (1), bladder (1), small bowel (1), and melanoma (1). The median time to hyperprogression was 67 (range 42-110) days, and the mean survival was 7.9 months from trial enrollment. We did not identify any clinical factor or specific CPI therapy that associated with hyperprogression. Exploratory biomarker analysis of genomic (gene panel assay) and immune subsets of tissue microenvironment (multiplex staining) is underway. Conclusions: This is the largest cohort investigated for hyperprogression across multiple cancers in literature. The rate of hyperprogression observed is less than previously reported in literature, and physicians need to be aware of this possibility while administering CPI to their patients.