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Lenalidomide Plus Rituximab Improves PFS Among Patients with FL and MZL
San Diego, California—Lenalidomide plus rituximab (R2) improves progression-free survival by 54% compared to single-agent rituximab for patients with relapsed or refractory indolent non-Hodgkin lymphoma (NHL), according to results from the phase 3 AUGMENT trial.
These findings were presented at the 2018 ASH Annual Meeting by John Leonard, MD, Meyer Cancer Center, Weill Cornell Medicine and NewYork Presbyterian hospital, New York.
The AUGMENT trial enrolled 358 patients, 82% with follicular lymphoma (FL) and 18% with marginal zone lymphoma (MZL). All patients were previously treated with 1 or more prior systemic therapies (median 1; range, 1-12), 84% received prior rituximab and 51% had prior antilymphoma therapy within 2 years of enrollment.
Patients were stratified based on prior rituximab treatment, time since last antilymphoma therapy, and histology. Patients were then randomized 1:1 to R2 or rituximab plus placebo (control) for up to 1 year. Patients assigned to the R2 regimen received oral lenalidomide 20 mg/day, days 1-21 in 28-day cycles for 12 cycles plus rituximab intravenously 375 mg/m2 weekly in cycle 1 and day 1 of cycles 2-5. Patients in the control group received rituximab and placebo on the same schedule.
The primary endpoint of the trial was progression-free survival (PFS) based on 2007 IWG criteria without PET as assessed by independent review committee (IRC). Secondary endpoints included overall response rate (ORR), complete response (CR), duration of response (DOR), time-to-next antilymphoma treatment, overall survival (OS), and safety.
At a median follow-up of 28.3 months, the median PFS was 39.4 months for patients receiving the R2 regimen versus 14.1 months for control. IRC-assessed ORR was 36.6 and 21.7 months for the R2 and control arms, respectively. The time-to-next antilymphoma treatment for R2 versus control with a hazard ratio (HR) of 0.54 (95% confidence interval [CI], 0.38 – 0.78; P = 0.0007). OS data were not mature with 16 deaths reported in the R2 arm versus 26 deaths in the control arm (HR = 0.61 [95% CI, 0.33 - 1.13]).
All grade treatment-related adverse events of interest that were more common with R2 versus control were infections (63% vs 49%), cutaneous reactions (32% vs 12%), constipation (26% vs 14%), thrombocytopenia (15% vs 4%), and tumor flare reaction (11% vs 1%). Grade 3/4 adverse events were reported in 69% of patients in the R2 arm and 32% of patients in the control arm. Grade 5 adverse events were reported in 2 patients from each arm.
Treatment-related adverse events leading to discontinuation of lenalidomide occurred in 9% of patients in the R2 arm versus 5% in the control arm, with neutropenia being the only adverse event leading to discontinuation of lenalidomide in 5 patients. Overall 71% of patients receiving the R2 regimen completed all 12 cycles of treatment and 61% of patients completed treatment in the control group. The leading cause of discontinuation among both groups was disease progression.
“R2 demonstrated superior efficacy over rituximab monotherapy (plus placebo) as measured by the primary endpoint of progression-free survival as well as secondary endpoints of ORR, CR, DOR, and TTNLT [time-to-next antilymphoma treatment] in patients with R/R FL grade 1-3a and MZL,” concluded Dr Leonard and colleagues.
“R2 represents an important new treatment option in patients with previously treated FL/MZL, with meaningful advantages over single-agent rituximab,” they added.
Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: A Phase III Randomized Study of Lenalidomide Plus Rituximab (R2) Vs Rituximab/Placebo in Patients with Relapsed/Refractory Indolent Non-Hodgkin Lymphoma. Presented at: the 60th ASH Annual Meeting and Exposition; December 1-4, 2018; San Diego, CA. Abstract 445.
