Nine-year follow-up of lenalidomide plus rituximab as initial treatment for mantle cell lymphoma.

Although chemoimmunotherapy is the current standard of care for initial treatment of mantle cell lymphoma (MCL), newer data suggest that there may be a role for a chemotherapy-free approach. We report the 9-year follow-up results of a multicenter, phase 2 study of lenalidomide plus rituximab (LR) as the 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 of 92% in evaluable patients, with 64% achieving a complete response. At a median follow-up of 103 months, 17 of 36 evaluable patients (47%) remain in remission. The 9-year progression-free survival and overall survival were 51% and 66%, respectively. During maintenance, hematologic adverse events included asymptomatic grade 3 or 4 cytopenia (42% neutropenia, 5% thrombocytopenia, and 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, and 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, whereas the remainder were noninvasive skin cancers treated with local skin-directed therapy. Two patients permanently discontinued therapy because of concerns of 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. This trial was registered at www.clinicaltrials.gov as #NCT01472562.