ALBERT

Description: Rituximab proved to be effective in relapsed and refractory indolent NHL as a single agent and generated impressive results in phase II studies in combination with chemotherapy. In a prospective randomized trial we compared the efficacy and toxicity of rituximab (375 mg/m² d 1) plus MCP-chemotherapy ( mitoxantrone 8 mg/m² d 3 + 4, chlorambucile 3 x 3 mg/m² d 3 – 7, prednisolone 25 mg/m² d 3 – 7 ) given every 28 days for a total of 8 cycles versus MCP (d 1 – 5) x 8 cycles alone in advanced indolent NHL and MCL. Efficacy endpoints included overall and complete response rates, event free survival, progression free survival, overall survival and toxicity. For response assessment classical definitions have been used. Between 10/98 and 09/03 we randomized 358 patients (pts) with advanced stage follicular lymphoma (FL) (grade 1 + 2), lymphoplasmacytic lymphoma and MCL to either R-MCP or MCP. The study arms are well balanced for all demographic factors. 201/358 pts (56%) had FL. Both regimens were well tolerated with a low incidence of serious adverse events. The overall response rate (RR) and the complete response rate (CR) for all pts was 85,5% and 42% in the R-MCP arm versus 65,5% and 20% in the MCP arm (p

Description: Background: Clinical superiority of R-MCP (rituximab, mitoxantrone, chlorambucil, prednisolone) vs. MCP alone in patients with advanced stage indolent Non-Hodgkin’s-Lymphoma was demonstrated in a prospective, randomized, controlled, multicenter clinical trial (n=358). Data on resource utilization were collected alongside this clinical trial. Objective: To evaluate the health economic consequences, i.e. total cost and cost-consequences, of R-MCP vs. MCP from the perspective of a German payer (statutory sickness fund). Methods: Resource utilization data on 329 patients were collected and analyzed for the treatment phase (8 month). In addition, an interim analysis of the first 3 years of the subsequent observation period (planned: 7 years) was conducted. Data on resource utilization for initial chemotherapy, chemotherapy administration, treatment of adverse events, treatment of complications/progressive disease, subsequent chemotherapies and treatment for other reasons were collected. Several sensitivity analyses were performed to address different cost environments (e.g. treatment at university hospital vs. municipal hospital vs. private practice) and discounting scenarios. Results: Mean cost of the treatment phase in the base case analysis was EUR 35,890 for R-MCP (95%CI: EUR 33,178 – 38,602 and EUR 21,508 MCP per patient (95%CI: EUR 17,703 – 25,314). More treatment cycles were administered in the R-MCP arm (1,026 MCP, 1,237 R-MCP). Mean cost per active treatment cycle was EUR 4,932 for R-MCP (95%CI: EUR 4,512 – 5,353) and EUR 3,270 for MCP (95%CI: EUR 2,619 – 3,922). Mean (undiscounted) cost per patient in the observation period amounted to EUR 9,973 for R-MCP (95%CI: EUR 6,015 – 13,931) and EUR 15,896 for MCP (95%CI: 13,407 – 18,385). Mean observation time, after end of active treatment, was similar in both arms, 28.5 months for R-MCP, 27.5 months for MCP. Costs for treatment of adverse events, new chemotherapies and other reasons were reduced by 23%–39%, cost for treatment of progressive disease by 76% in the R-MCP arm compared to MCP alone. Extrapolating data to a full 3-year observation period results in savings of EUR 8,214 per patient with R-MCP compared to MCP alone. This compensates approx. 60% of the higher costs from the treatment phase. Clinically, R-MCP resulted in an objective response rate of 85.6% vs. 65.5% with MCP. After two years, based on Kaplan Maier estimate, event free survival for R-MCP was 69% vs. 44% for MCP alone (p〈 0.001) (For more detailed clinical results see abstract by Herold et al.) Conclusion: Initial treatment costs with R-MCP were EUR 14,382 higher compared to MCP alone. However, approx. 60% of additional costs are regained during the first three years after therapy due to savings for subsequent treatments, particularly for progressive disease. Combined with the clinical superiority of R-MCP, a favorable cost-effectiveness ratio may be expected when more mature data are available.