Assessment of Response to Immunotherapy in Patients with Hodgkin Lymphoma: Towards Quantifying Changes in Tumor Burden Using FDG-PET/CT

Immune checkpoint inhibitors are currently the standard of care for many advanced solid tumors, and they have been recently approved for the treatment of relapsed/refractory Hodgkin lymphoma and primary mediastinal B cell lymphoma. Assessments of the response to immunotherapy may be complicated by the occurrence of the flare/pseudoprogression phenomenon, consisting of initial tumor enlargement and even the appearance of new lesions, followed by a response, which may initially be indistinguishable from true progression. There have been efforts to characterize and capture the new patterns of response observed during immunotherapy, namely, pseudoprogression and delayed response, and several immune-related response criteria have been proposed. Confirming progression on a subsequent scan and measuring the total tumor burden are both common in immune-related criteria. Due to the peculiarity of hematologic malignancies, lymphoma-specific immune-related criteria have been developed (LYRIC), and they have been evaluated in research studies in comparison to the Lugano Classification. In this review work, we illustrate the evolution of the response criteria in lymphomas from the first CT-based criteria to the development of the PET-based Lugano Classification, further refined to take into account the flare phenomenon encountered during immunotherapy. We also describe the additional contribution of PET-derived volumetric parameters to the interpretation of responses during immunotherapy.