Comparing The Cost-Effectiveness Of Rituximab Maintenance (MR) and Radioimmunotherapy (RIT) Consolidation Therapy Following First-Line Chemo/Immunochemotherapies For Follicular Lymphoma

Follicular lymphoma (FL), the most common indolent non-Hodgkin's lymphoma, has been regarded incurable and no consensus in management strategy has existed so far. In current clinical practice, the most commonly used frontline therapy is the immunochemotherapy (R-chemotherapy). Several phase III randomized trials - ECOG1496(Hochster, JCO2009), PRIMA(Salles, Lancet2011), and FIT(Morschhauser, JCO2008) - have shown that rituximab maintenance (MR) therapy and radioimmunotherapy (RIT) consolidation in addition to the frontline R-chemotherapy can improve progression-free survival (PFS) and help achieve a higher response quality. We conducted a cost-effectiveness analysis of maintenance or consolidation therapy versus observation after frontline treatment from the US payer's perspective.

We developed separate Markov models over patients' lifetime for PRIMA, ECOG, and FIT trial to compare the cost and effectiveness of observation with MR/RIT after completion of frontline treatment. Published progression free survival (PFS) and overall survival (OS) curves were extracted and fitted with Log-logistic regression survival model. Progression risks and cause-specific mortality after first-line treatment were extrapolated from the corresponding fitted PFS and OS model for each arm. Risk estimates after second-line treatment were identical for different models, estimated from the published survivals of observation arm in EORTC20981 trial. Costs for administration, monitoring, and management of adverse events were based on Medicare reimbursement rates for physician services, and drug costs were the wholesale acquisition cost, all valued in 2013 US dollars. In the microsimulation, initial age at diagnosis was sampled from the age distribution according to Surveillance Epidemiology and End Result (SEER) database. All costs and effectiveness were discounted at 3% per year. Primary outcomes were incremental cost per life-year gained (LY) and cost per quality adjusted life-year (QALY) gained. Model robustness in parameter uncertainties were addressed by one-way and probabilistic sensitivity analysis.

Compared with observation, MR therapy provided 0.998 QALYs (0.901 LYs) at a cost of $43234 in PRIMA study, 1.070 QALYs (0.866 LYs) at a cost of $50146 in ECOG study, while RIT consolidation provided 0.795 QALYs (0.653 LYs) at a cost of $46085 in FIT trial. The incremental cost per QALY gained for RIT in FIT, and MR in PRIMA and ECOG were $57975, $43301, and $46844, respectively. From the table summarizing effectiveness and cost results, RIT and MR had comparable incremental QALYs before first progression, while RIT had higher incremental costs of adverse events due to relatively high incidence of adverse events in the RIT arm.

We used the same modeling framework and consistent parameter estimates to evaluate the cost-effectiveness of MR and RIT compared to observation after frontline treatment for FL patients. All strategies showed favorable cost-effectiveness profile with ICER below $100,000/QALY willingness-to-pay. Differences in induction therapies in three trials should also be noted when the ICERs of three models are compared.

Flowers:Abbott, Celgene, Millennium/Takeda, Sanofi, Spectrum, Janssen: Research Funding; Celgene, Genentech Bio-oncology : Consultancy.