In patients with indolent relapsed or refractory non-Hodgkin lymphoma (NHL), the addition of lenalidomide to rituximab may be associated with improved progression-free survival (PFS) compared with placebo plus rituximab, according to results from the phase 3 AUGMENT trial (ClinicalTrials.gov identifier: NCT01938001) published in the Journal of Clinical Oncology.
Usually, patients with indolent NHL respond well to frontline immunochemotherapy. If a patient relapses, rituximab is often administered as a monotherapy, though previous research suggests the addition of lenalidomide, an immunomodulatory drug, to rituximab could increase rituximab’s activity.
The phase 3 AUGMENT trial was a multicenter, randomized trial that enrolled 358 patients with relapsed or refractory follicular lymphoma or marginal zone lymphoma. Patients were enrolled at 97 centers in 15 countries and received either rituximab with lenalidomide (178 patients) or rituximab with placebo (180 patients). Administration of lenalidomide or placebo occurred for 12 cycles of 4 weeks; administration of rituximab occurred once per week in cycle 1 and on the first day of cycles 2 through 5.
At a median follow-up of 28.3 months, patients in the lenalidomide arm experienced a median PFS of 39.4 months (95% CI, 22.9-not reached) compared with 14.1 months (95% CI, 11.4-16.7) in the placebo arm. The hazard ratio for the lenalidomide arm was 0.46 (95% CI, 0.34-0.62; P <.001).
Some adverse events were more common in the lenalidomide arm: 63% of patients experienced infections, 58% experienced neutropenia, and 32% experienced cutaneous reactions, whereas in the placebo arm, 49% experienced infections, 23% experienced neutropenia, and 12% experienced cutaneous reactions.
Grade 3 or 4 neutropenia was observed in 50% of patients receiving lenalidomide and 13% of patients receiving placebo. Grade 3 or 4 leukopenia was observed in 7% of patients receiving lenalidomide and 2% of patients receiving placebo. All other grade 3 or 4 adverse events had differences in rate of no more than 5% between the 2 treatment arms.
“The magnitude of [difference in] efficacy between the 2 treatments is clinically meaningful and suggests that lenalidomide plus rituximab should replace rituximab monotherapy as a standard of care for patients with relapsed or refractory indolent NHL,” concluded the authors.
1. Leonard JP, Trneny M, Izutsu K, et al. AUGMENT: A phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma [published online March 21, 2019]. J Clin Oncol. doi:10.1200/JCO.19.00010