Cost-effectiveness of interferon alfa-2b added to chemotherapy for high-tumor-burden follicular non-Hodgkin's lymphoma

Recent data from GELF (Groupe d'Etude des Lymphomes Folliculaires) have sho wn that the addition of interferon alfa-2b (IFN) to a doxorubicin-containin g regimen (CHVP: cyclophosphamide, doxorubicin, teniposide and prednisone) prolongs both progression-free survival and overall survival in high-tumor- burden follicular non-Hodgkins lymphoma. This gain must be weighed against the incremental toxicity and cost of IFN over CHVP alone and the objective here was, to determine the marginal cost-effectiveness of additive IFN in t he spe cific setting of high-tumor-burden follicular non-Hodgkin`s lymphoma . Meta-analysis of GELF trial results employing a Markov model was used wit h three health states: No Progression, progressive Disease, and Death. Trea tment response. survival and toxicity data are drawn from the GELF study. T he current study is bused on the final analysis of 242 patients (J Clin Onc ol 1998:16:2332-2338). with a six year median follow-up for overall surviva l (median overall survival: not reached for CHVP+IFN vs 5.6 years for CHVP Only, p = 0.008). Measurements: Quality of life data (utilities) are taken from studies with similar dosing of IFN, from Q-TwiST (quality adjusted tim e without symptoms or toxicity) analysis of the GELF data and from a panel of experts gathered to develop treatment models for high-tumor-burden folli cular non-Hodgkin's lymphoma. Gusts and quality-adjusted years of life save d were discounted at 3% per annum. Setting: Costs determined for university medical centers in the United States. Results showed that, at the median cohort age of 52, IFN add 9.9 qualify-ad justed months at an added cost of $13,900 (marginal cost-effectiveness of $ 16,900 per quality-adjusted lire year, or QALY). A more complex, two-stage model approximates the actual cohort survival curves much better than a sim ple, one-stage model, but both models yield essentially the same marginal c ost-effectiveness. Sensitivity analysis to quality of life on IFN shows mar ginal cost-effectiveness ranging from $15,200/QALY (no penalty for IFN) to $21,300/QALY (20% quality adjustment, greater than that reported). The mode l is: quite insensitive to the probability of IFN toxicity. The model is mo derately sensitive to the efficacy of IFN in delaying progression, particul arly in the first 18 months (pProgI), but the marginal cost-effectiveness d oes not rise to $50,000/QALY until pProgI increases. 220% from the baseline . Although the model is moderately sensitive to the cost of IFN (cIFN), mar ginal cost-effectiveness is below %50,000/QALY for values of cIFN below $25 80/month (baseline cIFN = S850/month, corresponding to a marginal cost-effe ctiveness of $16,900/QALY in the baseline case). If the model is modified t o reflect the 14% overall survival advantage at five years found in trials utilizing more intensive initial chemotherapy (including the GELF trial), t hen the marginal cost-effectiveness drops to $11,900/QALY in the baseline c ase. In condusion, based on data from the GELF study. low-dose interferon a lfa-2b is cost-effective when added to CHVP therapy in the treatment of hig h-tumor-burden follicular non-Hodgkin's lymphoma. The analysis is robust: t he model employs very conservative assumptions, and additive IFN remains co st-effective over wide ranges of variables in sensitivity analyses. The mar ginal cost-effectiveness is best expressed as being in the range of $12,000 /QALY to $17,000/QALY in the baseline case. A simple Markov model can be us ed to describe treatment regimens with dis liner periods of therapy.