Augmenting Indolent Lymphoma Treatment Options With the Combination of Lenalidomide and Rituximab
Mené sur 358 patients atteints d'un lymphome indolent réfractaire ou récidivant, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout du lénalidomide au rituximab
Multiple analyses have described improved outcomes in indolent non-Hodgkin lymphoma, due in part to the development of anti-CD20 therapy and supportive care measures allowing for the administration of combination chemotherapy. In the case of follicular lymphoma, outcomes from large treatment centers estimate a median survival of nearly two decades with these advances.1,2 Similar improvements have been observed for most patients with marginal zone lymphoma as well.3 However, significant heterogeneity still exists within these entities. The historic subdivisions of follicular lymphoma on the basis of the fraction of intratumoral large cells and the divisions in marginal zone lymphoma on the basis of involved anatomic sites partially explain differences in outcomes. However, recent observations highlighting disparate survival on the basis of timing of progression require additional explanation. Patients able to achieve a prolonged treatment-free interval after diagnosis or after initial chemoimmunotherapy have outcomes similar to the background population.4 In contrast, survival for patients experiencing early events is markedly inferior.5,6 As such, this latter group needs better therapeutic options, especially with mechanisms of action distinct from standard of care.
Lenalidomide is an immunomodulatory agent with pleotropic immune and antiproliferative effects initiated via binding of the E3 ligase protein cereblon.7 In combination with rituximab, laboratory data suggesting an augmentation of antilymphoma effects with the addition of rituximab were supported by clinical trials results. Randomized phase II results in relapsed refractory patients demonstrated 53% and 76% overall response rates for lenalidomide and lenalidomide plus rituximab, respectively, with a median time to progression improving from 1 to 2 years as well.8 When administered to patients with previously untreated indolent lymphoma, a 3-year progression-free survival (PFS) of 79% to 81% was reported for the doublet. (...)
Journal of Clinical Oncology , éditorial en libre accès, 2018