ICML 2017: Phase IIIb MAGNIFY Study of Lenalidomide and Rituximab Combination in Relapsed/Refractory Follicular and Marginal Zone Lymphoma
An interim analysis of MAGNIFY, a phase IIIb, randomized, open-label, multicenter study of the R2 combination regimen (lenalidomide [Revlimid] plus rituximab [Rituxan]) in patients with relapsed or refractory marginal zone lymphoma, was presented at the International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland. This analysis expanded upon data presented earlier in the month at the ASCO Annual Meeting (Abstract 7502).
The MAGNIFY study continues to evaluate the clinical activity of 12 cycles of R2 combination therapy followed by randomization to either 18 cycles of R2 maintenance or 18 cycles of rituximab monotherapy, in patients with relapsed or refractory follicular lymphoma, marginal zone lymphoma, or mantle cell lymphoma. Approximately 500 patients are planned to be enrolled in the study.
The primary endpoint is progression-free survival. Secondary endpoints include overall survival, overall response rate, complete response, improvement of response, duration of response, duration of complete response, time to next lymphoma treatment, time to histologic transformation, safety, and exploratory quality-of-life measures. Enrollment in the MAGNIFY study is ongoing.
ASCO Data
At the ASCO Annual Meeting, interim data were presented from an analysis of a subset of patients from the MAGNIFY study with relapsed or refractory follicular lymphoma (n = 160) with early-relapse (n = 52) and double-refractory (n = 50) disease.
At the January 9, 2017, data cutoff, the 1-year progression-free survival for all follicular lymphoma patients was 70%, with 65% for double-refractory patients and 49% for early-relapse patients. Additionally, evaluable follicular lymphoma patients (n = 128) had an overall response rate of 66% with a complete response/complete response–unconfirmed rate of 38%. For double-refractory patients (n = 42), overall response rate was 45% with a complete response/complete response–unconfirmed rate of 21% and for early-relapse patients (n = 43), overall response rate was 47% with a complete response/complete response–unconfirmed rate of 21%. Median duration of response was not met at a median follow-up of 10.2 months.
The most common grade 3 or 4 adverse events observed in the study for all follicular lymphoma, double-refractory, and early-relapse patients, respectively, were neutropenia (29%, 42%, 37%), fatigue (6%, 4%, 8%), leukopenia (5%, 8%, 10%), thrombocytopenia (4%, 8%, 4%), and lymphopenia (3%, 6%, 4%).
ICML Data
Data presented at ICML in a separate analysis focused on patients with marginal zone lymphoma (n = 38), including nodal marginal zone lymphoma (n = 18), splenic marginal zone lymphoma (n = 10), and mucosa-associated lymphoid tissue lymphoma (n = 10).
At a median follow-up of 13.8 months from initiation of therapy with the R2 combination, evaluable patients with marginal zone lymphoma (n = 32) achieved an overall response rate of 66% with a complete response/complete response–unconfirmed rate of 44%. Evaluable nodal marginal zone lymphoma patients (n = 14) had an overall response rate of 57% with a complete response/complete response–unconfirmed rate of 57%. Evaluable splenic marginal zone lymphoma patients (n = 8) had an overall response rate of 63% with a complete response rate of 25%; and evaluable mucosa-associated lymphoid tissue lymphoma patients (n = 10) had an overall response rate of 80% with a complete response/complete response–unconfirmed rate of 40%. Median duration of response was not reached for any group.
The most common grade 3 or 4 adverse events observed in patients with marginal zone lymphoma were neutropenia (32%), thrombocytopenia (16%), and leukopenia (11%).
“The chemotherapy-free combination of lenalidomide and rituximab, with complementary mechanisms of action that are thought to enhance antibody dependent cellular cytotoxicity, continues to show encouraging activity and a tolerable safety profile in indolent lymphomas, and particularly in difficult-to-treat patient subsets,” said David J. Andorsky, MD, co–principal investigator of the study and medical oncologist at the Rocky Mountain Cancer Centers in Boulder, Colorado. “These results in patients who had failed multiple therapies or relapsed early, as well as the activity in marginal zone patients merit further study in this area of indolent lymphoma.”
About MAGNIFY
MAGNIFY is a phase IIIb, multicenter, open-label study of patients with grades 1–3b or transformed follicular lymphoma, marginal zone lymphoma, or mantle cell lymphoma who received at least 1 prior therapy and had stage I–IV, measurable disease. Approximately 500 patients are planned for enrollment in 12 cycles of R2 induction, with a projected 314 patients with at least stable disease after induction randomized (1:1) to 2 maintenance arms.
Induction includes oral lenalidomide at 20 mg/d, days 1–21 per 28-day cycle (d1–21/28) plus intravenous rituximab at 375 mg/m2, days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 3, 5, 7, 9, and 11 (28-day cycles). Patients are then randomized to maintenance lenalidomide at 10 mg/d, days 1 to 21/28, cycles 13 to 30, plus rituximab at 375 mg/m2, day 1 of cycles 13, 15, 17, 19, 21, 23, 25, 27, and 29 (R2, arm A), or rituximab alone (same schedule, arm B). Patients receiving R2 maintenance after 18 cycles may continue maintenance lenalidomide monotherapy at 10 mg/d, days 1–21/28 (per patient and/or investigator discretion), until disease progression as tolerated. Patients will be followed for ≥ 5 years after the last patient initiates induction therapy.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
