Early 18F-FDG PET/CT response predicts survival in Relapsed/Refractory Hodgkin Lymphoma treated with Nivolumab

: Anti-PD-1 monoclonal antibodies (anti PD-1 mAbs) such as nivolumab and pembrolizumab are associated with high response rates in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (HL). To date, no prognostic factor for overall survival (OS) has been established with these agents in HL. We examined whether the first early response assessment evaluated using 18F-Fluorodeoxyglucose PET/CT (ePET1), may be associated with OS in this setting. Methods: This retrospective study included 45 patients from 34 institutions. In a blinded, centralized review, three independent radiologists classified ePET1 obtained at a median of 2.0 months (interquartile range: 1.7-3.7 months) after nivolumab initiation using existing criteria (i.e., Lugano 2014, LYRIC 2016). Patients were classified at ePET1 according to 4 possible response categories: complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD). As the OS of patients with NMR and PMR were similar, they were grouped together. OS was estimated using the Kaplan-Meier method and compared between groups using log-rank testing. Results: Eleven patients (24%) died after a median follow-up of 21.2 months. The classification at ePET1 was identical between Lugano and LYRIC since all 16 progression events at ePET1 classified as indeterminate response per LYRIC were confirmed on subsequent evaluations. Both Lugano and LYRIC 2016 classified patients as CMR in 13 pts (29%), PMD in 16 pts (36%), NMR in 4 pts (9%) and PMR in 12 pts (27%). The 2-year OS [95CI] was significantly different in patients with PMD (0.53 [0.32-0.87]), NMR or PMR (0.80 [0.63-1.00]), and CMR (1.00 [1.00-1.00]) in the overall population (P = 0.02, n = 45 pts) as well as according to a landmark analysis at 3 months (P = 0.05, n = 32 pts). Conclusion: In R/R HL patients treated with anti PD-1 mAbs, ePET1 assessment using either Lugano or LYRIC predicts OS and allows early risk-stratification suggesting that ePET1 may be used to develop risk-adapted strategies.