Wiernik, P H

8560 Background: Lenalidomide has shown activity in a wide range of hematological malignancies. We conducted a phase II trial of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed or 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 1–21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary endpoint was overall response rate (ORR), with secondary endpoints of response duration, progression-free survival (PFS), and safety. Results: Forty-three patients were enrolled and were evaluable for response and safety. Patients had received a median of 3 prior systemic therapies (1–17) and half of all patients were refractory to their last therapy. The ORR was 23% (10/43), including a complete response (CR) or unconfirmed CR (CRu) rate of 7%. The median time to first response was 3.6 months (1.7–4.2) and the median time to CR or CRu was 4.2 months (1.9–11.1). Twenty-seven percent (6/22) of patients with follicular lymphoma grade 1 or 2, and 22% (4/18) of patients with small lymphocytic lymphoma responded to therapy. The median duration of response has not reached, but is longer than 16.5 months with 7 of 10 responses ongoing at 15–28 months. Median PFS was 4.4 months (2.5–10.4). Adverse events were consistent with the known safety profile of lenalidomide and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusions: Oral lenalidomide monotherapy produces durable responses with manageable side effects in relapsed or refractory indolent NHL and warrants further investigation in the treatment of indolent NHL. [Table: see text]

17569 Background: Lenalidomide is an immunomodulatory drug of the IMiD class that has activity in multiple myeloma, myelodysplastic syndromes and chronic lymphocytic leukemia. We report preliminary results of two Phase II studies assessing the safety and efficacy of lenalidomide monotherapy in subjects with relapsed/refractory indolent or aggressive non-Hodgkin’s lymphoma (NHL). Methods: Subjects with indolent (study NHL-001) or aggressive (study NHL-002) relapsed/refractory NHL following ≥ 1 prior treatment regimen with measurable disease are eligible. Subjects receive 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continue therapy for 52 weeks as tolerated until disease progression. Response and progression are evaluated using cross sectional imaging by the NCI criteria. Results: 10 subjects (2 indolent (I), 8 aggressive (A)) of a planned 80 (40 in each study) have enrolled thus far. Median age is 66 (45–80) and 7 subjects are female. Indolent histology is follicular center lymphoma grade 1, 2 (n = 2) and aggressive histology diffuse large cell lymphoma (n = 7) and follicular center lymphoma grade 3 (n = 1). Median time from diagnosis to lenalidomide monotherapy is 2.9 years (1.1–10) and median number of prior treatment regimens per subject is 3 (1–6). Median duration of follow-up is 2 months. Of eight subjects (2 I, 6 A) evaluable for response at two months, three demonstrated a decrease in their tumor burden by 72% (I), 68% (A) and 52% (A), two subjects (2 A) exhibited stable disease and three subjects (1 I, 2 A) had disease progression. Six of the ten subjects (2 I, 4 A) demonstrated no Grade 3 or 4 adverse events. Grade 3 or 4 hematological adverse events (neutropenia, thrombocytopenia) occurred in four subjects including one febrile neutropenia and one of these four subjects also exhibited Grade 3 cellulitis. No tumor flare or tumor lysis has been observed to date. Conclusions: Preliminary data of lenalidomide monotherapy in relapsed and refractory NHL are encouraging. [Table: see text]

8052 Background: Lenalidomide (Revlimid), an immunomodulatory drug of the IMiDs class, is approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. This study was designed to assess the safety and efficacy of lenalidomide in patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed/refractory aggressive NHL with measurable disease after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Results: As of enrollment cut-off, 50 patients were enrolled and 49 received drug. Forty-one patients were evaluable for response. The median age was 65 (46–84) and 18 were female. Histology was diffuse large B-cell lymphoma [DLBCL] (n=21), follicular center lymphoma grade 3 [FL] (n=3), mantle cell lymphoma [MCL] (n=14) and transformed [TSF] (n=3). Median time from diagnosis to lenalidomide was 3.2 (0.4–32) years and median number of prior treatment regimens was 3 (1–7). Fourteen patients (34%) exhibited an objective response (5 complete responses unconfirmed (CRu) and 9 partial responses (PR)), 12 had stable disease (SD) for a tumor control rate (TCR) of 63% and 15 progressive disease (PD). Responses were seen in each of the aggressive histologic subtypes studied: DLBCL (5/21), MCL (6/14), FL (2/3), and TSF (1/3). Five of 11 patients (45%) with a prior stem cell transplant responded. Progression free survival although ongoing is currently > 239 (>191 - >373) days in patients experiencing CRu and > 160 (>54 - >251) days in patients with PR. Most common Grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%) while most common Grade 3 adverse events were neutropenia (22%), leukopenia (14%) and thrombocytopenia (12%). Conclusion: Lenalidomide oral monotherapy is active with manageable side effects in relapsed/refractory aggressive NHL. No significant financial relationships to disclose.