Real-world analysis of immune checkpoint inhibitor efficacy and response predictors in patients treated at the CCCMunichLMU outpatient clinic

Abstract

Abstract Prediction of response to checkpoint inhibition (ICI) and immune related adverse events (irAEs) remain a challenge in the immunotherapy of solid tumors. To better understand the real-world clinical courses under ICI and identify possible predictive markers for response and irAEs, we retrospectively collected and analysed data from our interdisciplinary CCCMunich LMU outpatient clinic. We analysed the clinical course, standard laboratory parameters and staging results of 342 patients who received ICI therapy in the interdisciplinary outpatient clinic of the CCCMunich LMU between January 2015 and November 2020. Initial response to ICI was defined as complete response, partial response, stable disease or mixed response with treatment continuation in the second radiologic staging after start of therapy. Median age of the included patients was 67 years (25–89). More male patients received ICI on our outpatient ward than female patients (67.8% vs. 32.2%). The most common entities were urothelial carcinoma (21.3%) and bronchial carcinoma (19.6%), followed by renal cell carcinoma (18.7%), and head and neck tumors (10.8%). 24.6% of patients were initial responders. Patients who did not respond to ICI therapy had lower leukocyte, lymphocyte, monocyte, and neutrophil counts before treatment start compared to initial responders. The consolidation of these laboratory parameters into a score could not accurately predict initial response or progression-free survival (PFS). IrAEs occurred in approximately one-third of all included patients. The main side effects in patients expierencing irAEs were thyroiditis (20.5%), pneumonitis (16.4%), hepatitis (15.8%), and dermatological side effects (11.0%). Patients experiencing irAEs had a significantly longer PFS than patients without irAEs. Side effects were more frequent and severe in patients treated with combined ICI. Autoimmune disorders were not associated with more frequent occurrence of irAEs. This retrospective analysis illustrates the real-world use of ICI in clinical practice. With only 24.6% of patients responding to ICI, the clinical need for predictive markers is obvious and standard laboratory parameters such as white blood cell counts may become part of a comprehensive score to predict response and adverse events.