In the R2 arm of this study, 55% patients experienced grades 3 and 4 neutropenia. With a median age of presentation for both follicular lymphoma and MZL of over 60 years, oncologists should remain aware of this potentially fatal complication, especially in the frail, the elderly, and previously treated individuals who may have a high risk of myelosuppression. Clinicians should be prepared to rapidly adopt strategies of dose interruption, dose reduction, and growth factor use, as implemented in the trial. Of note, despite the high rates of severe neutropenia, only 3% of the participants experienced febrile neutropenia, and 71% patients in R2 group and 61% in rituximab group completed planned protocol therapy. Growth factor use was high at 36% in the R2 group, which may have been responsible for a lower incidence of febrile neutropenia.
Increased toxicities of tumor flare, rash, and constipation were observed in the R2 arm. Patients with greater than grade 1 neuropathy were excluded. For those at risk of thromboembolism, prophylactic anticoagulation or antiplatelet therapy was recommended in the trial. Lenalidomide dose was reduced to 10 mg for those with creatinine clearance of 30 to 59 mL/min.
The cost-effectiveness of lenalidomide/rituximab combination has not been fully studied against a sequential approach of using rituximab and lenalidomide for a limited number of cycles. The cost of a Revlimid 10-mg pill may be over $700.10 Costs associated with supportive care due to additional toxicities have not been quantified. For those with cost concerns or lack of insurance coverage, the R2 regimen may be cost prohibitive without financial assistance from charities.
Indolent NHL remains mostly incurable. The R2 approach is still not a curative one, and resources should be directed to investigate a cure for this population. Whenever feasible, participation in a clinical trial should be encouraged. Parameters have not been reported based on prognostic groups, and the study did not identify any biomarkers that may correlate with improved outcome. Perhaps a biomarker-based trial design may be most suitable in explaining the heterogeneity in follicular and marginal zone lymphomas.
—Rakesh Gaur, MD, MPH, FACP, Cancer and Blood Center at Kansas Institute of Medicine, Lenexa, KS