Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: A retrospective observational cohort study

e21524 Background: The association of objective imaging response with first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in a real-world context. We compared likelihood of objective response between patients receiving first line anti-programmed cell death protein 1 (anti-PD1) monotherapies (pembrolizumab or nivolumab), or combination nivolumab with the cytotoxic T-cell lymphocyte-antigen 4 inhibitor ipilimumab and outlined the association between objective response and baseline characteristics and survival outcomes. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from 2013-2020 in Alberta, Canada. Best imaging response was assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1. The primary outcome was likelihood of objective imaging response (complete or partial response) between patients receiving anti-PD1 monotherapy and those receiving combination nivolumab-ipilimumab. Secondary outcomes were the identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT) endpoints. Results: Of the 255 patients included, 49/255 (19.2%) had complete response 112/255 (43.9%) had partial response, 28/255 (11.0%) had stable disease, and 66/255 (25.9%) had progressive disease. Median OS was not evaluable (NE) (95% CI NE-NE) for complete responders, NE (95% CI 52.93 months-NE) for partial responders, 21.30 months (95% CI 15.20 months-NE) for stable disease, and 7.72 months (95% CI 5.77-10.6 months) for progressive disease (log rank p < 0.0001). A robust delineation of TTNT by imaging response was also seen. Likelihood of objective response was similar between patients treated with nivolumab-ipilimumab compared to those receiving anti-PD1 monotherapy (OR 1.87 95% CI 0.85-4.20, p = 0.124). Normal LDH level (OR 2.13; 95% CI 1.01-4.35, p = 0.047), non-mucosal primary site (OR 9.09; 95% CI 2.44-33.33, p < 0.001), and absence of BRAF V600E mutation (OR 3.23; 95% CI 1.39-7.69, p = 0.007) were independently associated with likelihood of objective imaging response in multivariable analysis. Conclusions: In this real-world analysis, we demonstrate no significant difference in likelihood of objective response between patients treated with anti-PD1 monotherapy and combination nivolumab-ipilimumab, and demonstrate that a normal LDH level, non-mucosal primary site, and absence of BRAF V600E mutation are associated with response. Imaging response was also strongly associated with both OS and TTNT irrespective of therapy received. These results may help inform treatment selection, and aid in counseling of advanced melanoma patients treated with first line ICI therapy in a routine clinical practice setting.