LUGANO, SWITZERLAND – The chemotherapy-free combination of lenalidomide (Revlimid) and rituximab was highly active as frontline therapy for patients with low- and intermediate-risk follicular lymphoma in a multicenter phase II trial.
Among 66 patients with previously untreated follicular lymphoma, the overall response rate to the combination was 95%, including complete responses in 72% of patients. The 5-year progression-free survival (PFS) rate was 70%, reportedof Weill Cornell Medicine, New York.
“I think this overall is a useful validation – confirmation of the single-center data that showed that this [combination] in a multicenter setting can be a highly effective and reasonably well-tolerated treatment approach for patients with untreated follicular lymphoma,” he said at the International Conference on Malignant Lymphoma, on behalf of colleagues in the National Cancer Institute Alliance for Clinical Trials in Oncology and Cancer and Leukemia Group B.
In the 50803 study, the investigators enrolled 66 treatment-naive patients. The median age was 53 years (range 32-79). Patients were eligible if they had grade 1-3a, stage 3-4 or bulky stage 2 untreated follicular lymphoma, with Follicular Lymphoma International Prognostic Index (FLIPI) scores of 0-2.
They received lenalidomide 20 mg/day on days 1 through 21 of each 28-day cycle for 12 cycles, plus rituximab administered once weekly for each week of cycle 1, and on the first day of cycles 4, 6, 8 and 10.
The investigators also evaluated polymorphisms in the Fc fragment of immunoglobulin G receptor IIa and IIIa (FcGR2A/FcGR3A).
One of the 66 patients never started treatment, leaving 65 for the response analysis.
As noted, the overall response rate was 95%, including 94% of 21 patients with FLIPI 0 or 1 disease, and 96% of 44 patients with FLIPI 2 or 3. There were no associations between FLIPI score and likelihood of achieving a complete response, and no associations between FcR polymorphism or change in angiogenic markers and either complete responses or PFS, Dr. Leonard said.
Complete responses, the primary endpoint, were seen in 15 of the 21 (71%) of patients with FLIPI 0-1, and in 32 of the 44 (73%) with FLIPI 2-3, for an overall complete response rate of 72%.
Partial responses occurred in 5 patients (23%) with FLIPI 0-1 and 10 patients (23%) with FLIPI 2-3, for an overall PR rate of 23%.
Respective rates of stable disease were 0, 2%, and 2%. One patient in each FLIPI group was not evaluated because of adverse events.
After a median follow-up of 5 years, the progression free survival rate was 70%.
The most common grade 3 or 4 adverse events were neutropenia, seen in 21% of patients, and infections, seen in 40% (including one grade 3 febrile neutropenia).
Grade 1-2 fatigue was reported by 51 patients, and grade 3 fatigue was reported by 4.
Other grade 3 or 4 events seen in more than 5% of patients included rash in 9%, and hyperglycemia, hypophosphatemia, or hypertension, each in 6% of patients.
Celgene and Genentech supported the study. Dr. Leonard has served as an adviser/consultant to Celgene and other companies.