Nine-year Follow-up of Lenalidomide Plus Rituximab as Initial Treatment for Mantle Cell Lymphoma.

While chemoimmunotherapy is the current standard of care for initial treatment of mantle cell lymphoma (MCL), newer data suggests that there may be a role for a chemotherapy-free approach. We report 9-year follow up of a multi-center phase 2 study of lenalidomide plus rituximab (LR) as initial treatment of MCL. The LR doublet is used as induction and maintenance until progression, with optional discontinuation after 3 years. We previously reported an overall response rate in evaluable patients of 92%, with 64% achieving a complete response. At a median follow up of 103 months, 17 (47%) of 36 evaluable patients remain in remission. The 9-year progression-free survival (PFS) and overall survival (OS) were 51% and 66%, respectively. During maintenance, hematologic adverse events (AEs) included asymptomatic grade 3 or 4 cytopenia (42% neutropenia, 5% thrombocytopenia, 3% anemia) and mostly grade 1 to 2 infections managed in the outpatient setting (50% upper respiratory infections, 21% urinary tract infections, 16% sinusitis, 16% cellulitis, 13% pneumonia, with 5% requiring hospitalization). More patients developed grade 1 and 2 neuropathy during maintenance therapy (29%) than during induction therapy (8%). Twenty-one percent of patients developed secondary malignancies including 5% with invasive malignancies, while the remainder were non-invasive skin cancers treated with local skin-directed therapy. Two patients permanently discontinued therapy due to concerns for immunosuppression during the COVID-19 pandemic. With long-term follow up, LR continues to demonstrate prolonged, durable responses with manageable safety as initial induction therapy.