(ChemotherapyAdvisor) – Combining lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) is active and “warrants further investigation,” a study concluded in the Journal of Clinical Oncology published online on December 26, 2012.

“This phase 2 study is the first to our knowledge to demonstrate the effectiveness of lenalidomide combined with rituximab in patients with relapsed or refractory CLL,” noted corresponding author Alessandra Ferrajoli, MD, of the Department of Leukemia at the University of Texas M. D. Anderson Cancer Center in Houston, TX. “The majority of responders remained on lenalidomide therapy until failure of therapy or lack of tolerance.”

The study enrolled 59 patients (42 to 82 years of age) who had received prior fludarabine-based therapy or chemoimmunotherapy. Each received intravenous rituximab 375 mg/m2 weekly during cycle 1 and on day 1 of cycles 3–12; each cycle was 28 days. Oral lenalidomide 10 mg was administered beginning on day 9 of cycle 1 and daily continuously thereafter.

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“Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely if patients benefitted clinically,” Dr. Ferrajoli noted.

The overall response rate (ORR) was 66%, including seven (12%) complete responses, seven (12%) nodular partial remissions (PRs), and 25 (42%) PRs; two patients (3%) had flow cytometry-negative CRs. “A majority of patients had achieved an objective response (PR or better) by three cycles of therapy, whereas all CRs were observed to occur after 12 or more cycles of therapy,” they wrote.

For patients with chromosome 17p deletion, the ORR was 53%, compared with 70% for those without 17p deletion; this difference was not significant (P=0.35). Prior response to fludarabine correlated with treatment response; ORR was 70% among patients not refractory to their last fludarabine-containing regimen versus 33% among those refractory to fludarabine (P=0.041).

The median time to treatment failure for all patients was 17.4 months (95% CI, 11.9 to 23.0 months). Median overall survival had not been reached. The investigators estimated survival at 36 months to be 71% (95% CI, 59% to 83%).

The most common grade 3 or 4 toxicity, occurring in 73% of patients, was neutropenia. 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,” they reported.

Noting the 66% ORR makes the lenalidomide/rituximab combination comparable to currently used chemotherapy combinations, “we plan to further evaluate the activity of this combination as initial therapy for patients unfit for chemoimmunotherapy and as a partner for novel agents,” Dr. Ferrajoli concluded.