Tumor flare reactions and response to lenalidomide in patients with refractory classic Hodgkin lymphoma

Patients with Hodgkin lymphoma (HL) failing salvage stem cell transplantation are candidates to investigational strategies. Lenalidomide represents an attractive option as it targets several signaling pathways, which regulate survival of HL cells and their microenvironmental interactions. We report the occurrence of Grades 2 and 3 tumor flare reactions in the first three patients entered a lenalidomide-based compassionate program for treatment-refractory HL. Flares occurred in concomitance of the scheduled week-off lenalidomide and upon withdrawal of symptomatic steroid treatment, and were associated with changes in B-cell regulatory cytokines and the concurrent expansion of polyclonal B-cells. Flares mimicked tumor progression but were effectively managed with anti-inflammatory treatment and followed by a clinical response, suggesting that they may mirror the pleiotropic actions of lenalidomide on HL microenvironment.