Rituximab (Rituxan) maintenance and radioimmunotherapy consolidation after front-line therapy with rituximab have favorable cost-effectiveness in the treatment of follicular lymphoma, found Qiushi Chen, PhD, of the H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology, Atlanta, and colleagues.
There is currently no consensus for the management of follicular lymphoma, the most common indolent non-Hodgkin lymphoma, but in current practice, rituximab is the most frequently used front-line therapy. Phase 3 randomized trials have demonstrated that rituximab maintenance and radioimmunotherapy consolidation after front-line rituximab improve progression-free survival (PFS).
In a cost-effectiveness analysis comparing maintenance or consolidation therapy versus observation after frontline treatment, the investigators developed Markov models from the phase 3 studies showing efficacy of either approach in the treatment of follicular lymphoma. These studies included the Primary Rituximab and Maintenance (PRIMA) trial, ECOG-1496, and the First-Line Indolent Trial (FIT); the risk estimates after second-line treatment were estimated from survival data in the observation arm of the EORTC-20981 trial.
In the PRIMA study, patients treated with induction therapy with rituximab and chemotherapy were randomly assigned to either maintenance rituximab or to observation. Two years of rituximab maintenance improved PFS from 57.6% in the observation group to 74.9% in the rituximab maintenance group. ECOG-1496 found that 2 years of maintenance rituximab improved 3-year PFS to 68% compared with 33% in the observation arm.
FIT evaluated consolidation with yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) in patients with advanced-stage follicular lymphoma in first remission; PFS was extended to 36.5 months in the radioimmunotherapy arm versus 13.3 months in a control arm.
The costs for drug administration and monitoring, as well as the management of adverse events were based on Medicare reimbursement rates for physician services, and drug costs were the wholesale acquisition costs, which were all valued in 2013 US dollars. The costs were also considered for grade 3 or 4 adverse events (hospitalization for infection/febrile neutropenia and outpatient costs for anemia, neutropenia, and thrombocytopenia). All costs and effectiveness were discounted at 3% annually.
The primary outcomes were incremental cost per life-year gained and cost per quality-adjusted life-year (QALY) gained.
“All strategies showed a favorable cost-effectiveness with ICER [incremental cost-effectiveness ratio] below $100,000 per QALY willingness to pay,” noted Dr Chen.
The total costs in the treatment arms were similar in the 3 studies, ranging from $116,288 in PRIMA to $128,295 in ECOG-1496 compared with $73,154 to $77,912 in the observation arms.
The adverse event costs were highest with rituximab ($3683, a result of having the highest rate of adverse events) compared with maintenance rituximab ($600) and radioimmunotherapy ($222).
Compared with observation, rituximab produced an additional 1.06 QALYs with an incremental cost of $41,066, for an incremental cost per life-year gained of $37,745 and an incremental cost per QALY gained of $38,742. The findings were similar for rituximab maintenance and radioimmunotherapy consolidation, with additional QALYs of 1.14 and 1.47, respectively, for incremental costs per life-year gained of $36,772 and $34,847, respectively, and incremental costs per QALY gained of $37,836 and $35,204, respectively.
Therapies were more costly and more effective than observation 95% to 99% of the time. An ICER of less than $100,000 per QALY was obtained 83% to 94% of the time, and an ICER of less than $50,000 per QALY occurred 65% to 78% of the time.