Cost Effectiveness Analysis of Rituximab Maintenance In Patients with Untreated High Tumour Burden Follicular Lymphoma After Response to Immunochemotherapy: A UK National Healthcare Services Perspective.

The PRIMA Phase III study demonstrates that rituximab (R) maintenance therapy after induction immunochemotherapy in previously untreated follicular lymphoma (FL) significantly improves progression-free survival (PFS) with little additional toxicity (Salles et al., 2009). Utilising clinical evidence from PRIMA, this economic analysis evaluated whether R-maintenance therapy in FL patients after response to R-chemotherapy induction is a cost-effective option compared to observational (Obs) practices in the UK National Healthcare System.

METHODS: A transition state (Markov) model was developed with FL patients having a complete/partial response to 1^st line R-chemotherapy induction being assigned across 4 health states reflecting their disease status; progression-free in 1^st line maintenance (PF1), progression-free in 2^nd line, progressive disease (PD) or Death. The model was developed over a 25 year horizon to capture the lifetime of an average patient. This required extrapolation of PFS beyond the PRIMA trial follow-up period (median 38.37 months; PFS hazard ratio 0.55; 95% CI [0.44-0.68]; Clinical Study report addendum) using the best parametric fit (Gompertz). The monthly probability of dying in PF1 was based on the maximum of either the observed PFS deaths in PRIMA or background mortality. The disposition of 1^st line R-maintenance patients after progression was based on ESMO guidelines (Dreyling et al., 2010) and PRIMA. Due to extensive censoring of overall survival in PRIMA (95% and 97% in the respective R and Obs arms), the probabilities of progressing or dying in second-line or third line were obtained from the EORTC 20981 trial (van Oers et al., 2010). Predicted time in each health state was weighted using FL utility scores (Pettengell et al. 2008) to account for quality of life and estimate the Quality Adjusted Life Years (QALYs).

Costs associated with the average dose of R-maintenance, post-progression treatments and managing grade 3/4 adverse events observed in PRIMA were incorporated into the relevant health state. Drug administration, patient monitoring and pharmacy costs were informed by expert opinion and the NHS schedule of reference costs.

RESULTS: The average overall survival in the 1^st line R-maintenance cohort was projected to be 1.27 years longer on average than in the Obs cohort (10.31 vs 9.05); and associated with an additional 1.17 QALYs. This is largely due to patients treated with 1^st line R-maintenance spending more time in progression-free in first line (1.17 years). Total costs were £14,129 higher in the 1^st line R-maintenance than the Obs arm and were driven by the cost of the study drug and its administration. However, this was partially compensated by the lower costs of rituximab therapy in 2^nd line (cost saving £198) and the lower costs of supportive care incurred at disease progression (cost saving £906).

The incremental cost-effectiveness ratios (ICERs) for 1^st line R maintenance was £14,712 Life Year Gained and £15,983 per QALY gained, well below an assumed willingness to pay threshold of £30,000. Although there is uncertainty associated with the progression of FL and relapse treatment costs, the ICER did not exceed £21,155 per QALY despite a wide variation in each parameter value used in both the probabilistic and deterministic sensitivity analysis.

CONCLUSIONS: The cost-effectiveness of R-maintenance in FL patients after response to R-chemotherapy is well within the acceptable willingness to pay ceiling and remains valid under most plausible sensitivity scenarios. This provides adequate reassurance that the superior clinical benefits of 1^st line R-maintenance are sufficient to justify the additional costs over observational practice.

Papadakis:F. Hoffmann-La Roche Ltd: Employment. Boyer:F. Hoffmann-La Roche Ltd: Employment. Bashir:F. Hoffmann-La Roche Ltd: Employment. Ball:F. Hoffmann-La Roche Ltd: Employment. Aultman:F. Hoffmann-La Roche Ltd: Employment. Carr:F. Hoffmann-La Roche Ltd: Employment.