San Diego, CA—Maintenance therapy with lenalidomide (Revlimid) after frontline chemotherapy markedly prolonged progression-free survival (PFS) in patients with high-risk chronic lymphocytic leukemia (CLL), according to interim results from a phase 3 study presented at the 2016 American Society of Hematology meeting.
Patients randomized to receive maintenance therapy with lenalidomide as part of the German CLL M1 clinical trial had a reduction in the risk for disease progression of more than 80% compared with placebo after a median follow-up of 17.5 months.
The Data Safety Monitoring Board “assessed results of this interim analysis as statistically significant and reliable in favor of lenalidomide. This is the first study to show the benefits of lenalidomide maintenance in this patient population,” said Anna Maria Fink, MD, Center of Integrated Oncology Cologne-Bonn, German CLL Study Group, University Hospital of Cologne, Germany, who presented the study results.
Further investigation is required to determine how lenalidomide maintenance therapy will fit into the treatment paradigms that use newer targeted therapies, Dr Fink said.
Study Results
This double-blind study randomized 89 patients with CLL (median age, 64 years) who achieved a partial response or better after frontline chemoimmunotherapy, but who were at high risk for disease progression, to lenalidomide maintenance therapy or to placebo in a 2:1 ratio. At the time of treatment randomization, patients had high-risk features, including deletion (del)17p (11.4%), TP53 mutation (20.5%), unmutated IGHV gene status at baseline (90.2%), high level (37%) of minimum residual disease (MRD), and intermediate MRD level (63%).
Lenalidomide maintenance therapy was initiated at 5 mg daily in the first 28-day cycle, escalating in 5-mg increments until MRD was achieved, with a target dose of 15 mg in the seventh cycle. If well-tolerated, lenalidomide was administered until disease progression. If after 18 cycles of treatment MRD levels remained at ≥10–4, lenalidomide 25 mg daily was permitted, starting at cycle 19.
Frontline chemotherapy included a combination of rituximab (Rituxan) and bendamustine (Treanda) or fludarabine (Fludara, Oforta) plus cyclophosphamide in approximately 60% of patients. Overall, 87% of patients achieved a partial response, and 9% achieved a complete response.
At the time of presentation, patients in the lenalidomide group received a median of 11.1 treatment cycles compared with 8.3 cycles in the placebo group.
After a median follow-up of 17.7 months, the median PFS was 32.3 months for high-risk patients who received lenalidomide maintenance therapy versus 3.7 months with placebo. For patients with intermediate-risk CLL, the median PFS was not reached in the lenalidomide group versus 19.4 months in the placebo group. The hazard ratio for PFS was 0.148 (P <.00001) in favor of lenalidomide.
No difference in the overall survival was reported between the 2 maintenance treatment arms: only 3 deaths occurred in this study. Approximately 8% of patients with MRD converted to negative MRD (no MRD) with lenalidomide maintenance therapy compared with no patients who received placebo.
Treatment was discontinued in 42.9% of patients who received lenalidomide and in 72.4% of patients who received placebo; the primary reasons were adverse events in the lenalidomide group (32.1%) and disease progression in the placebo group (44.8%).
Treatment is ongoing in 32 patients in the lenalidomide group and in 8 patients in the placebo group. Overall survival is planned to be analyzed by study completion in 2021.