High total metabolic tumor volume on 18F-FDG-PET/CT correlates with lack of immune response in advanced melanoma patients treated with pembrolizumab.

IntroductionAdvanced Melanoma is a known for its poor long-term prognosis and although the last few years an enormous improvement is seen due to the Immune Checkpoint Inhibitors (ICI), only a subset of patients (pts) benefit. Biomarkers to predict and guide treatment decisions are being investigated. The idea is that in tumorleasions with an immunosuppressive tumor micro-environment (TME) the ICI may not work, and that the lesions will become much larger. In this study we aimed to investigate the role of pre-treatment 18F-FDG PET/CT as a predictor of survival after pembrolizumab treatment.
MethodsOutcome data of 69 pts with advanced melanoma treated with pembrolizumab at the university hospital in Brussels were collected as part of a prospective therapeutically non-interventional trial. Objective responses were evaluated using the immune-related response criteria. Total Metabolic Tumor Volume (TMTV) and the Total Lesional Glycolysis (TLG) were measured, using MIM Encore Software®. A log rank was performed to correlate TMTV, TLG, LDH and presence of brain metastasis to overall survival (OS) and progression free survival (PFS) after pembrolizumab administration. Multivariate analysis was conducted for selected parameters. For each parameter, treshold values were determined to dichotomize the patients, prior to analysis.
Results/DiscussionFor all 69 pts, median PFS was 19 w and median OS was 130 w. A threshold of 90 mL of TMTV was identified as most optimal to distinguish a patient subpopulation with significantly worse PFS (median 7 w [95% CI 4-9] vs 56 w [95% CI 0-118]; HR 19.10, p<0.001) and OS (median 21 w [95% CI 2-41] vs not reached; HR 46.14, p<0.001). Also in a multivariate analysis (Cox multivariate logistic regression), the TMTV above 90 mL showed the strongest correlation with shorter PFS and shorter OS. Besides TMTV, the presence of brain metastasis was an independent factor associated with shorter PFS and OS. For TLG, similar patterns but with weaker correlations were detected.ConclusionsTMTV above 90 mL was the best predictive parameter to identify patients who did not respond to pembrolizumab monotherapy. This threshold could reflect a tumor volume, above which the patient’s immune system is unable to become activated. In such patients, other cancer treatments or combination immunotherapy might be better options. Confirmation of our findings is currently ongoing in an additional patient cohort.
AcknowledgementMarleen Keyaerts is a senior clinical investigator of the Research Foundation Flanders.