18F-FDG PET and CT Scans Detect New Imaging Patterns of Response and Progression in Patients with Hodgkin Lymphoma Treated by Anti-Programmed Death 1 Immune Checkpoint Inhibitor

The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo F-18-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti-programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. F-18-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective response at any time during the anti-PD1 treatment were classified as responders. Results: Sixteen relapsed or refractory classic HL patients were included. The median age was 39 y (age range, 19-69 y). The median previous lines of therapy was 6 (range, 3-13). The mean follow-up was 22.6 mo. Nine of 16 patients (56%) achieved an objective response. Two deaths occurred due to progressive disease at 7 mo. F-18-FDG PET/CT detected all responders at 3 mo and reclassified best overall response in 5 patients compared with CT alone. A decrease in tumor metabolism and volume (SUVmean, metabolic tumor volume) and increase in healthy splenic metabolism at 3 mo were observed in responders (area under the curve > 0.85, P < 0.04). Five of 16 patients (31%) displayed new imaging patterns related to anti-PD1; we observed 2 transient progressions consistent with indeterminate response according to the LYRIC (2016) (IR2b at 14 mo and IR3 at 18 mo) and 3 patients with new lesions associated with immune-related adverse events. Conclusion: Three-month F-18-FDG PET/CT scans detected HL patients responding to anti-PD1. New patterns were encountered in 31% of patients, emphasizing the need for further evaluation in larger series and close collaboration between imaging and oncology specialists on a per-patient basis.