Final Results of Calgb 50803 (alliance): a Phase 2 Trial of Lenalidomide Plus Rituximab in Patients With Previously Untreated Follicular Lymphoma
Year: 2017
Type: conference-abstract
Abstract: Background: In 2008 we initiated a multicenter phase 2 trial of lenalidomide and rituximab in patients (pts) with previously untreated follicular lymphoma (FL) and evaluated whether FcR polymorphisms and changes in circulating pro-angiogenic cell populations were associated with outcomes. Methods: Pts with untreated FL, grade 1-3a, stage 3-4 or bulky stage 2, FLIPI 0-2, were eligible. Treatment consisted of lenalidomide 20 mg/day on days 1-21 of a 28-day cycle for 12 cycles plus rituximab administered weekly x 4 on cycle 1 and day 1 of cycle 4, 6, 8, and 10. Polymorphisms in FcgR2A and FcgR3A were evaluated. Circulating endothelial cells (CEC), endothelial progenitor cells (EPC), and hematopoietic progenitor cells (HPC) were evaluated pre-treatment and at completion of therapy. The primary endpoint was complete response (CR). Results: Sixty-five pts started treatment and are included in this analysis. The median age was 53 y (range 32-79); 68% were FLIPI 0-1. Fifty-one pts (78.5%) completed 12 cycles of lenalidomide. Reasons for early termination included adverse events (n = 6) and patient refusal (n = 6) and disease progression (n = 2). Grade 3-4 neutropenia occurred in 21%. Infections occurred in 40%, including grade 3 infections in 9% and one (2%) grade 3 febrile neutropenia. Grade 1-2 and grade 3 fatigue were reported in 51 and 4 pts, respectively. Grade 1-2 and grade 3 rash were noted in 32% and 8% of pts, respectively. Other common adverse events included grade 1-2 diarrhea (38%), grade 1-2 constipation (25%), grade 1-2 nausea (25%), grade 1-2 arthralgia (22%). Grade 1-2 thromboembolic events were reported in 3 pts (5%). Notably, grade 3 tumor lysis syndrome was reported in two patients (3%) and grade 3 serum sickness was reported in one pt (2%). Overall, 62/65 (95%) of patients responded, including 72% CR (95% CI 60-83%). Mean CECs and HPCs decreased significantly compared to baseline (p < 0.01 in both), while EPCs remained stable (p = 0.88). There was no association between decrease in CEC/HPC or FcgR2A/FcgR3A polymorphism and CR. Sixteen pts have progressed, including 7 pts with a best response of CR, 8 of 9 patients with a best response of PR, and one with SD. With a median follow-up of 5 years, the 2-year, 3-year, and 4-year PFS were 86%, 81%, and 73%. There was no association between FLIPI and CR rate or PFS. Overall survival is 100%. Conclusion: In this multicenter phase 2 trial, lenalidomide plus rituximab yielded complete responses in 72% of pts with previously untreated FL, meeting the predefined criteria for a positive study. Seventy percent of all patients remain free from progression at 5 years. Keywords: follicular lymphoma (FL); lenalidomide; rituximab.
Source: Hematological Oncology
DOI: 10.1002/hon.2437_34
Authors: P. Martin, S. Jung, B. Pitcher, N.L. Bartlett, K.A. Blum, T. Shea, J. Ruan, S.E. Smith, J.P. Leonard, B.D. Cheson
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2624634944