Long-Term Health Outcomes and Costs Associated with the Use of Rituximab in Combination with fludarabine and Cyclophosphamide (R-FC) in the Treatment of relapsed or Refractory Chronic Lymphocytic Leukaemia (CLL) in Poland.

Results from the REACH (Robak et al, 2008) randomised clinical trial showed that patients with relapsed or refractory CLL who received rituximab in combination with fludarabine-cyclophosphamide (R-FC) experienced an additional ten months (median) without disease progression compared to those receiving FC alone (30.6 vs. 20.6 months). With the pressure on healthcare budgets, it has become increasingly important for decision makers to consider the value for money for treatments they reimburse. This analysis evaluated the life-time health outcomes and direct costs of R-FC compared to FC for relapsed /refractory CLL patients in Poland, using evidence from the REACH trial and the public payer perspective.

A cost-effectiveness analysis was conducted with patients modeled while in and transitioning through the health states; PFS, Disease Progression and Death. The best fit parametric function was used to extrapolate PFS beyond the end of the trial follow-up period (2.1 years) to a life-time horizon (15 years). The number of patients transitioning from PFS to death was based on the maximum of either the observed rate of death or background mortality. At the time of this analysis median overall survival had not been reached, thus a Markov process was used to model the transition from the progressed health state to death. Transitions from the progressive health state to death was based on a constant probability of dying calculated from the clinical data. Patients experiencing at least 1 day of progression were modeled using KM stratified by protocol-specified treatments to determine if the two populations were significantly different. No significant difference (p = 0.5596) was observed between the two population's progression to death and so the two populations were combined and modeled as a single population. The log of the survival was linearly regressed against time, with the estimated parameter serving as the statistic for the rate of death with respect to the exponential distribution. This rate of death was converted to a monthly probability of dying and applied to both arms.

Predicted time in each health state was weighted using CLL utility scores based on expert opinion to account for patient quality of life. Adverse events (≥grade 3), blood transfusions, bone marrow transplants, and subsequent CLL treatments collected prospectively in REACH were included in monitoring costs. Cost data were collected in 4 reference oncology centers and derived from the National Health Fund. According to Polish Health Technology Appraisal guidelines the costs were discounted by 5% and results by 3,5%.

When R-FC is compared to FC alone over a 15 year timeframe, the average benefit to the patient is 0.670 life years gained (LYG) and 0.585 quality-adjusted life years gained (QALY). For patients treated with FC alone their mean time to progression was 2.19 years compared with 3.11 years for R-FC treated patients. The main cost drivers for FC treated patients was cost of supportive care in progression. The total average per-patient cost is higher with R-FC when compared with FC alone, but partially offset by the lower mean supportive care cost of progression, bone marrow transplants and blood transfusions. Use of R-FC in place of FC alone is predicted to result in additional cost per extra LYG of 80 942 PLN (1EUR=4,1PLN), and cost per extra QALY of 91 283 PLN, on average. These incremental cost-effectiveness ratio (ICER) values were below the assumed willingness to pay threshold of 100 000 PLN, which is 3 times the Polish Gross Domestic Product (per capita, 2008). ICER values were found to be robust given the uncertainty associated with various parameters used to describe the disease progression of CLL.

R-FC is a clinically effective in the treatment of relapsed/ refractory CLL patients and demonstrates a strong case for being cost-effective compared to other treatments funded in Poland.

Robak:F Hoffmann-La Roche: Honoraria. Szkultecka-Dêbek:F.Hoffmann La Roche: Employment. Aultman:F Hoffmann-La Roche: Employment. Carr:F. Hoffmann La Roche: Employment.