Cost-Effectiveness Analysis of Frontline Polatuzumab-Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone And/or Second-Line Chimeric Antigen Receptor T-Cell Therapy Versus Standard of Care for Treatment of Patients with Intermediate- to High-Risk Diffuse Large B-Cell Lymphoma.

PURPOSE:Recent studies of polatuzumab vedotin and CD19 chimeric antigen receptor T-cell therapy (CAR-T) have shown significant improvements in progression-free survival over standard of care (SOC) for patients with diffuse large B-cell lymphoma. However, they are costly, and it is unclear whether these strategies, alone or combined, are cost-effective over SOC.METHODS:A Markov model was constructed to compare four strategies for patients with newly diagnosed intermediate- to high-risk diffuse large B-cell lymphoma: strategy 1: polatuzumab-rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) plus second-line CAR-T for early relapse (< 12 months); strategy 2: polatuzumab-R-CHP plus second-line salvage therapy ± autologous stem-cell transplant; strategy 3: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line CAR-T for early relapse; strategy 4: SOC (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus second-line salvage therapy ± autologous stem-cell transplant). Transition probabilities were estimated from trial data. Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from US and Canadian payer perspectives. Willingness-to-pay (WTP) thresholds of $150,000 US dollars (USD) or Canadian dollars (CAD)/QALY were used.RESULTS:In probabilistic analyses (10,000 simulations), each strategy was incrementally more effective than the previous strategy, but also more costly. Adding polatuzumab-R-CHP to the SOC had an ICER of $546,956 (338,797-1,199,923) USD/QALY and $245,381 (151,671-573,250) CAD/QALY. Adding second-line CAR-T to the SOC had an ICER of $309,813 (190,197-694,200) USD/QALY and $303,163 (221,300-1,063,864) CAD/QALY. Simultaneously adding both polatuzumab-R-CHP and second-line CAR-T to the SOC had an ICER of $488,284 (326,765-840,157) USD/QALY and $267,050 (182,832-520,922) CAD/QALY.CONCLUSION:Given uncertain incremental benefits in long-term survival and high costs, neither polatuzumab-R-CHP frontline, CAR-T second-line, nor a combination are likely to be cost-effective in the United States or Canada at current pricing compared with the SOC.