Cost-effectiveness and value of information analyses of Bruton's tyrosine kinase inhibitors in the treatment of relapsed or refractory mantle cell lymphoma in the United States.

Ibrutinib, acalabrutinib, and zanubrutinib have shown improvements in efficacy and safety over conventional chemoimmunotherapy in refractory or relapsed mantle cell lymphoma (R/R MCL). To evaluate the comparative cost-effectiveness of the Bruton's tyrosine kinase inhibitors (BTKIs) and estimate the expected value of (partial) perfect information (EV[P]PI) in terms of net health benefits (NHBs) and net monetary benefits (NMBs) forgone. Using a two-state Markov model (progression-free; progression or death), we estimated in base-case and probabilistic sensitivity analyses (PSAs) the incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) of, respectively, progression-free survival (PFS) life-years (PFLYs) and PFS quality-adjusted LY (PFQALY) gained (g) against 3-year and 5-year time horizons. A willingness-to-pay threshold of $150,000/PFQALY was used to assess the probability of being cost-effective in the PSA. EVPI was calculated from the respective NHBs and NMBs. Compared with ibrutinib, acalabrutinib yielded a 3-year ICER of $90,571 (PSA = $88,588)/PFLYg and ICUR of $117,098 ($110,063)/PFQALYg, whereas zanubrutinib yielded a 3-year ICER of $58,422 ($58,907)/PFLYg and ICUR of $73,027 ($73,634)/PFQALYg. The corresponding 5-year estimates were ICER of $73,918 ($74,189)/PFLYg and ICUR of $90,512 ($90,844)/PFQALYg for acalabrutinib and ICER of $48,641 ($48,732)/PFLYg and ICUR of $61,612 ($63,727)/PFQALYg for zanubrutinib. Compared with zanubrutinib, treatment with acalabrutinib yielded a 3-year ICER of $144,633 ($134,964)/PFLYg and ICUR of $197,227 ($166,109)/PFQALYg; the corresponding 5-year estimates were $117,579 ($118,161)/PFLYg and $136,144 ($136,818)/PFQALYg. The EVPI/patient was an NHB of 0.036 PFQALYs and NMB of $3,602 forgone, resulting in a population EVPI of $134,766,957 forgone. The EVPPIs/patient for effectiveness were NHB of 0.015 PFQALYs and NMB of $1,479, with corresponding values of 0.032 and $3,187 for costs and 0.015 and $1,519 for health-related quality of life forgone. This early cost-effectiveness analysis based on phase I/II clinical trials of BTKIs in R/R MCL suggests an additional PFS benefit for second-generation BTKIs compared with ibrutinib. However, the relative uncertainty due to the lack of direct trial evidence may lead to an opportunity cost or lost health benefits if the current evidence is adopted to compare between these products. Additional evidence is needed to address the relative efficacy of the BTKIs. A. McBride serves on speakers bureaus for Coherus BioSciences and Merck. He is now at Bristol-Myers Squibb in a position unrelated to this study. I. Abraham is joint equity owner in Matrix45. By company policy, owners and employees are prohibited from owning equity in client and sponsor organizations (except through mutual funds or other independently administered collective investment instruments), contracting independently with client and sponsor organizations, or receiving compensation independently from such organizations. Matrix45 provides similar services to biopharmaceutical, diagnostics, and medical device companies on a nonexclusivity basis. Of relevance to this article, Matrix45 has not provided any services to this study. I. Abraham is the quantitative methods editor of JAMA and deputy editor-in-chief of the The remaining authors have no relevant financial or nonfinancial interests to disclose.