Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 22; no. 6; pp. 382 - 392
• Main Authors: Greuter, MJE, Eertink, JJ, Jongeneel, G, Dührsen, U, Hüttmann, A, Schmitz, C, Lugtenburg, PJ, Barrington, SF, Mikhaeel, NG, Ceriani, L, Zucca, E, Carr, R, Györke, T, Burggraaff, CN, de Vet, HCW, Hoekstra, OS, Zijlstra, JM, Coupé, VMH
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022
• Subjects: Cost-Benefit Analysis; Duration of Therapy; FDG-PET; Health technology assessment; Humans; Interim response assessment; Lymphoma, Large B-Cell, Diffuse - diagnostic imaging; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - economics; Non–Hodgkin lymphoma; Positron-Emission Tomography; Treatment duration; FDG-PET; Interim response assessment; Health technology assessment; Treatment duration; Non–Hodgkin lymphoma
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2021.11.008

Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result. We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP. Strategies were evaluated separately in I-PET2 positive and I-PET2 negative patients. Outcomes included total costs and quality-adjusted life-years (QALYs) per patient (pp) from a societal perspective. Net monetary benefit (NMB) per strategy was calculated using a willingness-to-pay threshold of €50,000/QALY. Robustness of model predictions was assessed in sensitivity analyses. In I-PET2 positive patients, shortening treatment duration led to 50.4 additional deaths per 1000 patients. The STD strategy was less effective (-0.161 [95%CI: -0.343;0.028] QALYs pp) and less costly (-€2768 [95%CI: -€8420;€1105] pp). Shortening treatment duration was not cost-effective (incremental NMB -€5281). In I-PET2 negative patients, shortening treatment duration led to 5.0 additional deaths per 1000 patients and a minor difference in effectiveness (-0.007 [95%CI: -0.136;0.140] QALY pp). The STD strategy was less costly (-€5807 [95%CI: -€10,724;-€2685] pp) and led to an incremental NMB of €5449, indicating that it is cost-effective to shorten treatment duration. Robustness of these findings was underpinned by deterministic and probabilistic sensitivity analyses. Treatment duration should not be shortened in I-PET2 positive patients whereas it is cost-effective to shorten treatment duration in I-PET2 negative patients. Guideline recommendations for diffuse large-B-cell lymphoma treatment are shifting from long to short treatment duration. Using a Markov model, we evaluated the cost-effectiveness of this shortening in treatment duration, separately in I-PET positive and I-PET negative patients. We showed that this shift is justified for I-PET negative patients, but not for I-PET positive patients as shortening treatment duration in these patients has harmful consequences.