Abstract
BackgroundThe optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Active residual disease is considered prohibitive for treatment discontinuation and its detection by diagnostic CT imaging is limited. Here, we set out to determine the potential added value of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) to identify patients at higher risk of relapse following discontinuation of ICB in advanced melanoma.MethodsMetastatic melanoma patients who discontinued ICB were identified retrospectively. Eligible patients received FDG-PET and diagnostic CT within four months of ICB discontinuation. We defined morphologic response using RECIST v1.1. Complete metabolic response (CMR) was defined as uptake in tumor lesions below background, whereas any site of residual, FDG-avid disease was rated as non-CMR. The primary endpoint was time to progression (TTP) after therapy discontinuation stratified by morphologic and metabolic imaging response using Kaplan–Meier estimates and log-rank test.ResultsThiry-eight patients were eligible for this analysis. Median follow-up was 37.3 months since ICB discontinuation. Median TTP in the overall cohort was not reached. A greater proportion of patients were rated as CMR in PET (n = 34, 89.5%) as compared to complete response (CR) in CT (n = 13, 34.2%). Median TTP was reached in patients with non-CMR (12.7 months, 95%CI 4.4-not reached) but not for patients with CMR (log-rank: p < 0.001). All patients with complete response by CT had CMR by PET. In a subset of patients excluding those with complete response by CT, TTP remained significantly different between CMR and non-CMR (log-rank: p < 0.001).ConclusionAdditional FDG-PET at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone. Results may have clinical relevance especially for patients with residual tumor burden.
Highlights
The optimal duration of immune checkpoint blockade (ICB) therapy is not well established
Additional fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) at time of discontinuation of ICB therapy helps identify melanoma patients with a low risk of recurrence and favourable prognosis compared to CT imaging alone
This study investigated the value of FDG-PET to determine the potential added value of FDG-PET to further identify patients with residual morphologic disease and at risk of relapse following discontinuation of immunotherapy in metastatic melanoma
Summary
The optimal duration of immune checkpoint blockade (ICB) therapy is not well established. Immune checkpoint blockade (ICB) with programmed cell death protein-1 (PD-1) and/or cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors remarkably improved 5-year overall survival (OS) rates in patients with metastatic melanoma [1,2,3,4]. In the CheckMate 067 trial, 74% patients in the combined anti-PD-1 and anti-CTLA-4 treatment arm who were still alive after 5 years (n = 151) had discontinued immunotherapy and had not received subsequent systemic therapy [4]. Optimal duration of ICB treatment in patients with metastatic melanoma has not been defined yet. Most clinical trials evaluating PD-1 and PD-L1 inhibitors for metastatic melanoma did not limit duration of treatment and drugs were to be given until disease progression, unacceptable toxicitiy or withdrawal of consent [7]. Few clinical trials have observed patients who discontinued treatment after responding to therapy, and prospective studies exploring the optimal timing of treatment discontinuation have only recently started recruitment [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
