Comparison of PET-based criteria of evaluation of response to immunotherapy in patients with advanced melanoma.

Abstract

e21536 Background: Immune checkpoint inhibitors (ICI), such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1), have evolved as a dominant strategy in the treatment of metastatic melanoma (MM) in the last decade. At least three PET-based criteria are available for the early assessment of response to immunotherapy: PET/CT Criteria for Early Prediction of Response to Immune Checkpoint Inhibitor Therapy (PECRIT), PET Response Evaluation Criteria for Immunotherapy (PERCIMT) and European Organization for Research and Treatment of Cancer (EORTC) criteria. The aim of this study was evaluation of the concordance of different PET-based criteria for the assessment of response to immunotherapy and to assess their capability of properly stratifying patients in terms of overall survival (OS) and progression free survival (PFS). Methods: We retrospectively enrolled patients with the following inclusion criteria: diagnosis of MM, treatment with ICI for MM and tumor assessment performed by at least two [18F]F-fluorodeoxyglucose (FDG) PET/CT scans (a baseline and ad interim scan). [18F]F-FDG PET/CT scans were analyzed according to PECRIT, PERCIMT and EORTC criteria. Agreement was assessed using Fleiss' kappa and Cohen’s kappa. Prognostic curves of PET/CT response according to different criteria were evaluated in terms of PFS and OS by Kaplan-Meier estimates and were compared by log-rank test. Results: From December 2021 to January 2022, 30 patients were enrolled. 18/30 patients received nivolumab, 8/30 pembrolizumab, 3/30 ipilimumab and 1/30 the combination of nivolumab and ipilimumab. According to PECRIT criteria, 6 patients achieved complete metabolic response (CMR), 7 partial metabolic response (PMR), 5 stable metabolic disease (SMD) and 12 (40%) progressive metabolic disease (PMD). By PERCIMT criteria, 6 patients had response classified as CMR, 9 PMR, 8 SMD and 7 (23.4%) PMD. Finally, by EORTC criteria there were 6 CMR, 10 PMR, 2 SMD and 12 (40%) PMD. In 9 cases out of 30, one criteria assessment differed from the other two and in one patient each criteria evaluation differed from the others (PMD by PECRIT, SMD by PERCIMT, PMR by EORTC). The percentage of patients concordantly evaluated by the three criteria was 68% (Fleiss’ kappa = 0.68). PECRIT and EORTC criteria showed the highest agreement (Cohen’s kappa 0.719), followed by PERCIMT and PERCRIT (Cohen’s kappa 0.69). PERCIMT and EORTC showed 64.4% of concordance. Furthermore, all three criteria were successful in stratifying patients in terms of OS and PFS (p-value < 0.05). Conclusions: We observed substantial agreement among different PET evaluation criteria, with PECRIT and EORTC criteria showing the highest concordance. Analysis of a larger population is needed to prove the utility of PET response evaluation in early prognostic stratification.