Pietronigro, Dennis

SummaryPatients with aggressive non‐Hodgkin lymphoma (NHL) who relapse after autologous stem cell transplantation (ASCT) have a poor prognosis. Additional therapy is often poorly tolerated, and new treatment modalities are needed. This efficacy and safety study was a retrospective analysis of two phase II trials (NHL‐002 and NHL‐003) that studied single‐agent lenalidomide in patients with relapsed/refractory aggressive NHL with prior (n = 87) compared with no prior ASCT (n = 179). The overall response rate in the ASCT group was 39% [14% complete response (CR)], including 29% in patients with diffuse large B‐cell lymphoma, 63% in mantle cell lymphoma, and 60% in transformed lymphoma. The timing of transplant relative to receiving lenalidomide had no effect on outcomes. Median progression‐free survival for the ASCT group was 3·7 months (16·9 months for patients in CR; 7·3 months for partial responders) at a median 12·5‐month follow‐up. Median response duration was 7·9 months. Regardless of prior ASCT, lenalidomide monotherapy was efficacious in heavily pretreated patients with aggressive, relapsed/refractory NHL, with a safety profile that was consistent with prior studies of single‐agent lenalidomide.

PurposeLenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL).Patients and MethodsPatients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety.ResultsForty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively).ConclusionOral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.