Maintenance Therapy with Rituximab for Follicular Lymphoma Is Cost-Effective – A Canadian Perspective.
Authors: Maturi Bridget , Mikhael Joseph R. , Dunlop William C.N. , Tilden Dominic T. , Wong Lisa 
Published: October 2019

Abstract
Background: Rituximab maintenance therapy has been shown to significantly improve overall survival (OS) (p<0.0111) and progression free survival (PFS) (p<0.0001) compared to observation alone in patients with relapsed/refractory follicular lymphoma (van Oers MHJ et al, et al. Blood. 2006 [Epub ahead of print]).The objective of this analysis was to estimate the cost-effectiveness, from a Canadian perspective, of rituximab maintenance therapy versus observation alone (OA) in relapsed/refractory follicular lymphoma patients following response to induction therapy with or without rituximab, based on data from the European Organisation for Research and Treatment of Cancer (EORTC) 20981 study (Clinical Study Report 1016350).
Methods: The impact of rituximab maintenance therapy (375 mg/m2 every 3 months until progression or for 2 years) compared with OA was evaluated using a lifetime, health-state transition model. All patients entered the model following response to chemotherapy +/− rituximab as induction therapy (progression-free health state [PFHS]). The model simulates the movement of patients from PFHS to either progressed health state (PHS) or death based on the data from the study. PFS and OS following rituximab maintenance were extrapolated from 2-year Kaplan-Meier curves from the study data using a Weibull distribution. In the base case model, the PFS and OS benefits of rituximab maintenance therapy were conservatively assumed to last only 5 years. Quality of life utility values for the health states in the model were derived from a study of 165 patients using the EQ-5D questionnaire. Direct annual medical costs including drug acquisition, administration and preparation were estimated from published sources. All costs are reported in 2005 Canadian dollars (CAD). Costs and outcomes were discounted at a rate of 5%. In order to address uncertainty in point estimates, one-way sensitivity analyses were also performed.
Results: From the model, the estimated life-time incremental PFS for rituximab maintenance therapy was a 1.4 year increase over OA (3.1 vs 1.7 years). OS of rituximab maintenance patients was 0.9 years longer than in OA patients (5.6 vs 4.7 years). Total cost for rituximab maintenance therapy was estimated to be CAD34,748, with the majority of costs related to drug acquisition (CAD18,652). Rituximab maintenance resulted in a gain of 0.8 Quality Adjusted Life Years (QALYs) (4.0 vs [OA] 3.2 QALYs) at an incremental cost of CAD17,136. The incremental cost effectiveness ratio (ICER) of rituximab maintenance vs OA is, therefore, estimated to be CAD20,428 per QALY gained. The ICER of rituximab maintenance was sensitive to the duration of treatment benefit and frequency of subsequent treatment.
Conclusions: In patients responding to induction therapy, rituximab maintenance therapy improves overall survival and progression-free survival compared with observation alone. This pharmacoeconomic model demonstrates that maintenance therapy with rituximab is a cost-effective approach for the management of patients with follicular lymphoma.