High Response Rate to Lenalidomide in Relapsed/Refractory Aggressive Non-Hodgkin’s Lymphoma with Prior Stem Cell Transplant.

Background: High dose chemotherapy with stem cell transplant is currently employed in relapsed/refractory aggressive Non-Hodgkin’s Lymphoma (NHL). Lenalidomide (Revlimid®), an immunomodulatory drug, has shown activity in hematological malignancies including relapsed/refractory multiple myeloma, chronic lymphocytic leukemia and cutaneous T-cell lymphoma.

Aim: To determine the activity and safety of lenalidomide monotherapy in relapsed/refractory aggressive NHL following stem cell transplant (SCT).

Methods: Patients with relapsed/refractory aggressive NHL with measurable disease ≥ 2 cm 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: Fourteen (29%) of the 49 patients enrolled into the study had a prior SCT. Median age was 61 (23–76) and 5 were female. Histology was diffuse large B-cell lymphoma [DLBCL] (n=5), follicular center lymphoma grade 3 [FL] (n=2), mantle cell lymphoma [MCL] (n=5) and transformed [TSF] (n=2). Median time from diagnosis to lenalidomide was 3.9 (1.1–31.4) years and median time from SCT to study entry was 1.9 (0.5–11.7) years. The median number of prior treatment regimens was 5 (2–8). Seven patients (50%) exhibited an objective response (1 complete response unconfirmed (CRu), and 6 partial responses (PR)), 5 had stable disease (SD) and 2 patients had progressive disease (PD). Six responses were in eight patients having a tumor burden < 50 cm² and a time since last rituximab therapy of ≥ 230 days. One response was achieved in six patients having a tumor burden ≥ 50 cm² or a time since last rituximab therapy of < 230 days. Four of 6 (67%) patients who had SCT as their last treatment prior to lenalidomide [median time from SCT to lenalidomide = 0.8 (0.5–4.8) years] responded. Progression free survival [PFS] is 4.5 months and ongoing. Six patients (43%) required at least one dose reduction with a median time to first dose reduction of 1.6 months (0.4–4.9). Two patients each (14%) had Grade 4 adverse events of neutropenia and thrombocytopenia. The most common Grade 3 adverse events were neutropenia (36%), thrombocytopenia (21%), and leukopenia (14%).

Conclusion: Lenalidomide produced a 50% response rate with manageable side effects in relapsed/refractory aggressive NHL following stem cell transplant.