NIMG-17CENTRAL NEUROPATHOLOGY REVIEW TO ASSIST IN THE EVALUATION OF IMMUNE-RELATED TREATMENT CHANGES VERSUS DISEASE PROGRESSION IN CHECKMATE-143

Abstract

BACKGROUND: Subsets of cancer patients treated with immune modulating therapies show progression using conventional response criteria before ultimately exhibiting objective responses and/or stable disease. This is particularly challenging in glioblastoma (GBM) trials since standard treatments may also be associated with pseudoprogression (RT/temozolomide) or pseudoresponses (bevacizumab) by imaging. To minimize premature discontinuation of immunotherapy in patients who may be demonstrating an immune-mediated tumor response, or correctly identify disease progression, direct histopathologic examination may be needed to inform management on these agents. METHOD(S): Central neuropathology review was incorporated into the CHECKMATE-143 trial to evaluate immune-related treatment effects versus disease progression. Patients with recurrent GBM in Cohort 1 (n = 20) were randomized 1:1 to receive nivolumab 3 mg/kg every 2 weeks (Q2W) or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks (Q3W) for 4 doses followed by nivolumab3 mg/kgQ2W. Patients who under went tumor biopsy for suspected progression after trial enrollment were eligible for central neuropathologic review of these post-treatment samples. Post-treatment samples were scored visually by two neuropathologists for percentage of necrosis/reactive changes and viable solid tumor. Any distinct morphological changes were also noted. Comparison was made to unrelated samples treated previously with RT/temozolomide. RESULT(S): Post-treatment samples were examined in 6 patients and all demonstrated immune treatment-related effects. Lymphocytic infiltrates were minimal. Characterization of the histopathology findings and treatment-effects will be reported. CONCLUSION(S): The challenges in distinguishing tumor progression from SOC or immune-related tumor necrosis, immune infiltrates and possible morphological changes at the tumor site highlight the importance of tissue re sampling and central neuropathology review to accurately assess for treatment-related changes. Immune-related treatment effects observed in this preliminary safety cohort suggest biologic activity of checkpoint inhibition at the GBM tumor site but minimal lymphocytic infiltration at the time point analyzed.