Early ¹⁸F-FDG PET/CT Response Predicts Survival in Relapsed or Refractory Hodgkin Lymphoma Treated with Nivolumab

Abstract

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 (ePET 1), 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 ePET 1 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 ePET 1 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 ePET 1 was identical between Lugano and LYRIC since all 16 progression events at ePET 1 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] probability was significantly different in patients with

PET/CT imaging for tumour response assessment to immunotherapy: current status and future directions

“…1) with improved clinical outcome [57]. In the setting of early treatment response of HL and anti-PD-1treatment, both Lugano criteria and LYRIC performed equally with equivocal findings [58], a result that possibly relates to the rather rare occurrence of pseudoprogression in HL [55,56,59].…”

Immunotherapy by Immune Checkpoint Inhibitors and Nuclear Medicine Imaging: Current and Future Applications

“…Thus, no pseudoprogression was reported in the two studies, including a total of 60 patients with refractory or relapsed Hodgkin lymphoma treated with immunotherapy and having an early therapeutic evaluation (2 to 3 months) by 18 F-FDG PET/CT [70,71]. Moreover, in a retrospective multicentric study including 45 patients with Hodgkin lymphoma treated by nivolumab, the classification at the 18 F-FDG PET performed at 2.0 months (interquartile range: 1.7-3.7 months) was identical between Lugano criteria and LYRIC, since all 16 progression events on this examination classified as an indeterminate response per LYRIC were confirmed as progressive diseases on subsequent evaluations [72]. In most other types of lymphoma, including follicular lymphoma and diffuse large B cell lymphoma, ICIs have been rarely used to date, because they are less effective, and therefore, there is a lack of data regarding their therapeutic evaluation [73].…”

Early Evaluation of Immunotherapy Response in Lymphoma Patients by 18F-FDG PET/CT: A Literature Overview

“…In this system, patients categorized as having an indeterminate response (IR) at initial imaging required repeat imaging within 12 weeks and a re-evaluation to determine if the original appearance represents true or pseudoprogression. Recent studies focusing on HL validated 18F-FDG PET/CT in early immunotherapy evaluation, stating that a semiquan-titative evaluation can distinguish responders from non-responders and confirming the leading role of metabolic response assessment in these patients [3,24,47,48]. PET/CT: DS 4 or 5 with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or EoT assessment.…”

“…In fact, studies comparing immune-related LYRIC criteria to conventional response criteria, pointed out that patients classified as indeterminate response (IR) by LYRIC criteria at the early assessment were subsequently confirmed as having true progression of metabolic disease (PMD) at the late evaluation [46]. As shown in the cohort studied from Chen et al, a trend towards worse overall survival (OS) was present in patients with type 2 IR according to LYRIC criteria [47]. Recently, a similar conclusion was carried out by Mokrane et al who hypothesized that the "wait-and-see" strategy recommended in other tumor types does not seem applicable at an early time point assessment in patients with R/R HL treated with immunotherapy [8].…”