Cost-Effectiveness of PET-Directed vs. Combined Modality Therapy for Early Stage Hodgkin Lymphoma

Abstract

The standard of care for early-stage Hodgkin Lymphoma (HL) is combined modality therapy (CMT) consisting of chemotherapy and involved site radiation therapy (ISRT). Due to concerns that the combination of chemotherapy and radiotherapy is more harmful than chemotherapy alone, several trials have assessed the impact of omitting radiation with the use of positron emission tomography (PET). PET is considered useful in identifying patients at low risk for disease recurrence. These studies have suggested a detriment in progression free survival (PFS) for patients who do not receive ISRT but similar overall survival. The purpose of this study was to compare the cost-effectiveness of PET-directed therapy vs. standard of care CMT. This economic evaluation used a cost-effectiveness model simulating 5-year outcomes for 1 million patients with early-stage HL treated with either PET-directed therapy consisting of 2 cycles of Adriamycin, Bleomycin, Vincristine, and Dacarbazine (ABVD) +/- 20 Gy ISRT or CMT consisting of 2 cycles of ABVD + 20 Gy ISRT. Patients entered the model with early-stage favorable HL and received either PET-directed therapy or CMT. Patients progressed to no evidence of disease (NED), disease progression (DP), or death. Patients with DP underwent salvage therapy with high dose chemotherapy and stem cell transplant (HDC-SCT). Health utilities were obtained from published studies and transition probabilities were derived from the GHSG HD16 trial. Costs were obtained from the Healthcare Bluebook and 2019 National Medicare fee schedules. For the base case analysis, we assumed 3-dimensional conformal radiation treatment. Utilities and costs were discounted at 3% annually. The primary outcome measured was the incremental cost-effectiveness ratio (ICER); we defined the willingness-to-pay (WTP) threshold at $100,000 per quality-adjusted life-year (QALY). Deterministic sensitivity analyses were performed to assess for uncertainty around model parameters. We found that PET-directed therapy and CMT strategies were associated with costs of $42,536 and $37,931, respectively. The CMT strategy was slightly more effective than the PET-directed therapy strategy with QALYs of 2.947 and 2.945, respectively. As CMT was both less expensive and more effective as compared to PET-directed therapy, CMT was the dominant strategy. On one-way sensitivity analyses, the model was most sensitive to costs of ABVD, ISRT, and HDC-SCT salvage treatment. Three-way sensitivity analyses showed that the model was also sensitive to the relative costs of these treatments. For patients with early-stage favorable HL requiring definitive treatment, CMT is the cost-effective strategy as compared with PET-directed therapy. These results should be used to inform the ongoing debate regarding the role of ISRT and PET in the treatment of early-stage favorable HL.