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Lenalidomide Approved: Follicular Lymphoma and Marginal Zone Lymphoma

Follicular lymphoma.

The FDA has approved lenalidomide (Revlimid®, Celgene Corporation) in combination with a rituximab product for relapsed/refractory follicular lymphoma (FL) and relapsed/refractory marginal zone lymphoma (MZL).

Follicular lymphoma is the most common form of indolent (slow growing) B-cell non-Hodgkin lymphoma (NHL), accounting for around 20% to 30% of all NHL cases. Marginal zone lymphoma, another type of indolent B-cell NHL, comprises approximately 8% of all NHLs.

"Current treatment options for recurrent FL include rituximab monotherapy, bendamustine, or other chemotherapy alone or with obinutuzumab or rituximab," state John P. Leonard, MD, of Weill Cornell Medicine and New York Presbyterian Hospital, and colleagues in their publication of AUGMENT (NCT01938001), one of the clinical trials on which the approval was based. "For many patients, the efficacy/toxicity tradeoffs of rituximab versus chemotherapy-based or kinase inhibitor regimens are major issues. There is clear rationale for adding lenalidomide to rituximab in relapsed patients with FL."

The AUGMENT study, published in the Journal of Clinical Oncology, randomly assigned 358 patients with relapsed/refractory FL or MZL in a 1:1 ratio to lenalidomide plus rituximab or placebo plus rituximab, with a primary end point of progression-free survival in the intent-to-treat population. Lenalidomide/rituximab increased median progression-free survival compared with rituximab alone (39.4 vs 14.1 months). It also produced a higher objective response rate, both in patients with FL (80% vs 55.4%) and in patients with MZL (65% vs 44%).

"The magnitude of efficacy differences between the two 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," conclude Dr. Leonard and colleagues.

For the other trial on which the approval was based, MAGNIFY (NCT01996865), 232 patients with grade 1 to 3a FL or MZL were administered 12 cycles of lenalidomide/rituximab prior to randomization to lenalidomide/rituximab or placebo/rituximab. Results were published in the Journal of Clinical Oncology for the initial phase of the trial, prior to randomization. In efficacy-evaluable patients, lenalidomide/rituximab produced overall response rates of 70% in patients with fewer than two lines of prior systemic anti-lymphoma therapies and 66% in those with two or more prior regimens. It produced complete response rates of 51% and 36% in the two groups, respectively, with one-year progression-free survival rates of 68% and 70% and duration of response rates of 77% and 81%. The median time to response was 2.8 months for both groups.

The AUGMENT trial found increased rates of infections (63% vs 49%), neutropenia (58% vs 23%), and cutaneous reactions (32% vs 12%) for lenalidomide/rituximab compared with rituximab alone. In addition, the lenalidomide/rituximab group experienced higher rates of grade 3/4 neutropenia (50% vs 13%) and leukopenia (7% vs 2%). The MAGNIFY trial reported the most common grade 3 or higher treatment-emergent adverse events as neutropenia, thrombocytopenia, and leukopenia. Across both trials, adverse reactions occurring in at least 20% of patients included neutropenia, fatigue, diarrhea, constipation, nausea, and cough. The prescribing information contains a boxed warning concerning the risks of embryo-fetal toxicity, hematologic toxicity, and life-threatening venous and arterial thromboembolism.

The recommended dose of lenalidomide in FL and MZL is 20 mg administered orally once daily on the first 21 days of a 28-day cycle for up to 12 cycles.

For More Information

Andorsky D, Coleman M, Yacoub A, et al (2018). Response rate to lenalidomide plus rituximab (R2) as independent of number of prior lines of therapy: interim analysis of initial phase of MAGNIFY phase IIIb study of R2 followed by maintenance in relapsed/refractory indolent NHL. J Clin Oncol, 36(suppl_15). Abstract 7516.

Clinicaltrials.gov (2018). Rituximab plus lenalidomide for patients with relapsed / refractory indolent non-Hodgkin's lymphoma (follicular lymphoma and marginal zone lymphoma) (AUGMENT). NLM identifier: NCT01938001.

Clinicaltrials.gov (2019). Lenalidomide plus rituximab followed by lenalidomide versus rituximab maintenance for relapsed/refractory follicular, marginal zone or mantle cell lymphoma. (MAGNIFY). NLM identifier: NCT01996865.

Leonard JP, Trneny M, Izutsu K, et al (2019). AUGMENT: A phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol, 37(14):1188-1199. DOI:10.1200/JCO.19.00010

Revlimid® (lenalidomide) prescribing information (2019). Celgene Corporation. Available at: https://media.celgene.com/content/uploads/revlimid-pi.pdf

Image credit: Patho. Licensed under CC BY-SA 3.0

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