Phase II study of lenalidomide maintenance after rituximab-methotrexatebased induction therapy in primary central...

Adults with primary central nervous system lymphoma (PCNSL) who are ineligible for consolidative whole-brain radiotherapy (WBRT) or autologous stem-cell transplantation (ASCT) due to advanced age, comorbidities, or impaired performance status have limited treatment options. Lenalidomide is active in relapsed PCNSL, but prospective data on its use as maintenance are limited. We conducted a multicenter phase II trial of lenalidomide maintenance in adults with PCNSL who achieved at least a partial response after 2-6 cycles of methotrexate- and rituximab-based chemoimmunotherapy and were not candidates for WBRT or ASCT. Lenalidomide 15 mg was given orally on days 1-21 of 28-day cycles for up to 12 cycles or until progression or toxicity. The primary endpoint was 2-year progression-free survival (PFS) from maintenance initiation. Thirty-one patients were enrolled (median age 72 years); 30 received lenalidomide with a median of 11 cycles, and 50% completed all 12. At a median follow-up of 20.7 months, the 2-year PFS was 58.8% (95% CI, 43.4-79.8%), exceeding the pre-specified alternative threshold of 55%, although the formal one-sample log-rank test did not reach statistical significance (p = 0.084). The 2-year overall survival was 83.9%. Grade 3-4 neutropenia occurred in 53.3%, whereas most non-hematologic adverse events were grade 1-2. Treatment was discontinued for toxicity in 13%; one grade 5 pneumonia occurred, and no thromboembolic events were observed. These findings suggest that lenalidomide maintenance is feasible and potentially beneficial in consolidation-ineligible PCNSL patients, though the hypothesis-generating nature of this single-arm study warrants confirmation in randomized comparative trials.