NIMG-16PSEUDOPROGRESSION AND IMMUNOTHERAPY IN GLIOBLASTOMA: A CASE SERIES FROM COHORT 1 OF CHECKMATE-143 (NCT02017717)

Abstract

BACKGROUND: In CHECKMATE-143, safety and tolerability of nivolumab and ipilimumab were evaluated in patients with first recurrence of glioblastoma. One of the challenges with immune targeting therapies is the accurate assessment of changes in disease progression with neuroimaging. Immune-related treatment effects presenting as temporary increases in target or non-target lesions or a transient appearance of a new lesion are observed in ∼10% of patients. These changes can result from influx of inflammatory cells leading to temporary appearances of increased mass. Here, we present neuroimaging results that meet RANO criteria for progressive disease, and the corresponding histopathology findings. METHODS: In cohort 1, eligible patients were randomized 1:1 to nivolumab 3mg/kg Q2W or nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W followed by nivolumab 3 mg/kg Q2W. Responses were assessed using RANO criteria at Weeks 6, 12, and Q8W onward. Treatment beyond progression was permitted until a second radiologic confirmation of progression 8 weeks later. At the time of imaging progression, if biopsy/resection was feasible, pathological evaluation was performed and histopathologic findings were correlated with imaging changes. RESULTS: A total of 20 patients were treated in cohort 1. In some cases, immune-related treatment effects presenting as target lesion growth or appearance of new lesions were observed on imaging. A variety of histopathologic patterns were observed with radiographic progression. Imaging and the correlated histopathological findings will be presented in detail. CONCLUSIONS: Immune-related treatment effects can occur in patients with glioblastoma receiving checkpoint inhibitors. Tissue acquisition and pathologic assessment can clarify the etiology of progression imaging findings preventing premature discontinuation of potentially beneficial therapy.