Determinants of the optimal first-line therapy for follicular lymphoma: a decision analysis

Abstract

Combination immunochemotherapy is the most common approach for initial therapy of patients with advanced-stage follicular lymphoma, but no consensus exists as to the optimal selection or sequence of available regimens. We undertook this decision analysis to systematically evaluate the parameters affecting the choice of early therapy in patients with this disease. We designed a Markov model incorporating the three most commonly utilized regimens (RCVP, RCHOP, and RFlu) in combinations of first- and second-line therapies, with the endpoint of number of quality-adjusted life years (QALYs) until disease progression. Data sources included Phase II and Phase III trials and literature estimates of long-term toxicities and health state utilities. Meta-analytic methods were used to derive the values and ranges of regimen-related parameters. Based on our model, the strategy associated with the greatest number of expected quality-adjusted life years was treatment with RCHOP in first-line therapy followed by treatment with RFlu in second-line therapy (9.00 QALYs). Strategies containing RCVP either in first- or second-line therapy resulted in the lowest number of QALYs (range 6.24-7.71). Sensitivity analysis used to determine the relative contribution of each model parameter identified PFS after first-line therapy and not short-term QOL as the most important factor in prolonging overall quality-adjusted life years. Our results suggest that regimens associated with a longer PFS provide a greater number of total QALYs, despite their short-term toxicities. For patients without contraindications to any of these regimens, use of a more active regimen may maximize overall quality of life.

Figure 1

Markov model schematic diagram. Exploratory model incorporating transformation is indicated by the addition of hatched arrows and the health state of “transformation.” Rx1, first-line therapy; Rx2, second-line therapy, Rx3, third-line therapy; Rem1, first remission; Rem2, second remission. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

Model diagnostics and validation. Unadjusted survival curves for each decision strategy were generated using a combined endpoint of third-line therapy or death.

Figure 3

Two-way sensitivity analysis. Each shaded region represents the combination of median PFS values at which a particular decision strategy is dominant. Axis ranges represent the range of values obtained from individual published studies. “X” indicates the specific PFS values derived from the meta-analysis. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]