R²: Preliminary Results of a Phase II Study of Lenalidomide and Rituximab in Relapsed/Refractory Indolent Non-Hodgkin’s Lymphoma (NHL)

Background: Lenalidomide (Revlimid®) is a potent immune-modulating, anti-angiogenic agent, approved in the USA for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with the 5q- chromosomal deletion. Lenalidomide also demonstrates activity as monotherapy in aggressive and indolent NHL, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and cutaneous T-cell lymphoma. The current study was designed to evaluate the safety and efficacy of the lenalidomide and rituximab (R²) combination in patients with relapsed/refractory indolent NHL.

Methods: Patients with relapsed/refractory indolent NHL with measurable disease after at least 1 prior treatment regimen were eligible. Lenalidomide was initially administered at a dose of 25mg orally once daily, on days 1–21 on a 28-day cycle, and continued until disease progression. Rituximab 375mg/m² was infused beginning on day 15 of cycle 1, and repeated weekly for a total of 4 doses. Following development of tumor lysis syndrome (TLS) in two patients, the protocol was amended to reduce the starting dose of lenalidomide to 20mg, and TLS prophylaxis was provided. Response and progression were evaluated using IWLRC methodology.

Results: At the time of this report, 7 patients were enrolled, and 6 had initiated therapy. The median age was 67 (range 54–91) years and 2 were female. Histologies are follicular lymphoma [FL] (n=5), SLL (n=1), and marginal zone lymphoma (n=1). Median time from diagnosis to treatment on study was 7.3 (3.3–19) years and median number of prior treatment regimens was 4 (1–5). All patients had received prior treatment with rituximab. Four patients were evaluable for response, all of whom had rituximab-resistant disease. All four evaluable patients, including two with highly refractory disease, after a median of 2 cycles, exhibited an objective response (1 complete response unconfirmed, 2 partial responses, and 1 minor response). Progression free survival, currently ongoing, is > 102 days. Toxicity included TLS in two refractory patients with FL within the first week of therapy. The most common grade 3 and 4 events were neutropenia, lymphopenia, and hyponatremia.

Conclusion: This is the first study to demonstrate that combination therapy using lenalidomide and rituximab is safe and active in relapsed/refractory indolent NHL. The side effect profile was acceptable with the addition of TLS prophylaxis. With additional analysis, the R² combination may warrant further study in refractory indolent lymphoma.