Recent studies have investigated the combinatory effect of lenalidomide plus rituximab, the R2 regimen, in patients with newly diagnosed and relapsed/refractory indolent Non-Hodgkin Lymphoma (iNHL) and mantle cell lymphoma (MCL).
Studies have demonstrated enhanced expansion and recruitment of natural killer (NK) cells targeting tumors, trafficking of activated immune cell subsets to the tumors and significant treatment efficacy (R2 having shown a greater efficacy in MCL and iNHL).
Although tolerability of these regimens is consistent across the studies, some cases of grade 3/4 adverse events have been reported. Optimal strategies managing these adverse events have been discussed in this review published in Annals of Oncology this month by J. Ruan et al. Lenalidomide alone or R2 are given in an outpatient setting and most of the dose-dependent AEs occur within the first cycles. Management of those AEs by the treating team is highly important to allow optimal treatment duration, with the goal of improving outcomes.
Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas
Lenalidomide is an oral immunomodulatory drug with significant activity in indolent B-cell and mantle cell lymphomas. Lenalidomide has a manageable safety profile whether administered as a single agent or in combination with rituximab. The combination of lenalidomide with rituximab, known as the ‘R2’ regimen, enhances efficacy over what has been shown with monotherapy and has demonstrated activity in patients considered resistant to rituximab. Tolerability of these regimens has been consistent among studies. Asymptomatic neutropenia is the most common grade 3/4 adverse event, typically managed by dose interruption, followed by dose reduction once neutrophils have recovered. Nonhematologic toxicities (e.g. fatigue) are generally low-grade, manageable with concomitant treatment, and/or lenalidomide dose modification. More frequent with R2, immune-related symptoms such as rash and tumor flare are important to recognize as lenalidomide-associated treatment effects in patients with lymphoma who require supportive care and potential dose modifications. Severe tumor flare reactions with painful lymphadenopathy are not typically observed outside of chronic lymphocytic leukemia/small lymphocytic lymphoma. Venous thromboembolism is uncommon in lymphomas, though prophylaxis is recommended. The general safety profile, differences between lenalidomide monotherapy and R2 treatment, and optimal strategies for managing adverse events are discussed here.
- Ruan J, et al. Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Annals of Oncology. 2016 Jul 27 (7):1226-1234. doi: 10.1093/annonc/mdw158. Epub April 6, 2016.