Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia

Abstract

Purpose: Lenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia (CLL). We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL.

Patients and methods: Fifty-nine adult patients (age 42 to 82 years) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab. Patients had received prior fludarabine-based therapy or chemoimmunotherapy. Rituximab (375 mg/m(2) intravenously) was administered weekly during cycle one and on day 1 of cycles three to 12. Lenalidomide was started on day 9 of cycle one at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely if patients benefitted clinically.

Results: The overall response rate was 66%, including 12% complete responses and 12% nodular partial remissions. Time to treatment failure was 17.4 months. Median overall survival has not been reached; estimated survival at 36 months is 71%. The most common grade 3 or 4 toxicity was neutropenia (73% of patients). Fourteen patients (24%) experienced a grade 3 to 4 infection or febrile episode. There was one episode of grade 3 tumor lysis; one patient experienced renal failure during the first cycle of therapy, and one venous thromboembolic event occurred during the study.

Conclusion: The combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation.

Trial registration: ClinicalTrials.gov NCT00759603.

Fig 1.

Kaplan-Meier overall (OS) and failure-free survival curves for all study patients. (A) OS and time to treatment failure (TTF) for all patients receiving lenalidomide and rituximab (n = 59), with median 33 months of follow-up. (B) OS for responding patients (complete [CR] or partial response [PR], n = 39) compared with nonresponders (stable or progressive disease, n = 20). (C) TTF according to pretreatment fluorescent in situ hybridization by Döhner cytogenetic hierarchy. (D) TTF by refractoriness to fludarabine. (E) TTF by cytogenetic risk group and prior fludarabine response; patients with 17p deletion and refractory to last fludarabine therapy (n = 6) are compared with patients with only one of these high-risk features (ie, fludarabine refractory or del(17p), n = 15) and patients without these high-risk features (n = 38). (F) OS by cytogenetic risk group and prior fludarabine response comparing the same patient subgroups as in (E); patients who were fludarabine refractory but had no 17p deletion and patients who had 17p deletions but were not refractory to fludarabine had TTF and OS similar to those in patients with neither of these high-risk features; patients who had 17p deletions and were also refractory to fludarabine had significantly shorter TTF and OS compared with all other patients.

Fig A1.

Time to first response and response duration with lenalidomide and rituximab. Individual patients are graphed on ordinate, and time measured in cycles of therapy on abscissa. Gray bars demonstrate time without objective response (stable disease [SD]/nonresponse [NR]); gold bars indicate partial response (PR) or nodular PR; blue bars indicate complete response (CR). Open triangles represent loss of response off therapy; solid triangles represent loss of response on therapy. Open chevrons demonstrate continued response off therapy; solid chevrons demonstrate continued response on therapy. Solid diamonds demonstrate treatment cessation because of death.