Cost-Effectiveness of Bruton Tyrosine Kinase Inhibitors for the Treatment of Relapsed or Refractory MCL

Second-generation Bruton tyrosine kinase inhibitors (BTKis) acalabrutinib and zanubrutinib may provide additional progression-free survival (PFS) among patients with relapsed or refractory mantle cell lymphoma (MCL) when compared with first-generation BTKi ibrutinib, according to an early cost-effectiveness analysis (J Manag Care Spec Pharm. 2022;28(4):390-400; doi:10.18553/jmcp. 2022.28.4.390). This finding may have resulted because second-generation BTKis were developed to be more selective and specific for the Bruton tyrosine kinase receptor and to cause fewer off-target side effects than ibrutinib.

“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,” wrote Ivo Abraham, PhD, Center for Health Outcomes and PharmacoEconomic Research, University of Arizona, Tucson, AZ, and colleagues.

Dr Abraham and colleagues sought to evaluate the comparative cost-effectiveness of the BTKis and estimate the expected value of perfect or partial perfect information regarding net health benefits and net monetary benefits forgone. A two-state Markov model was used to predict progression-free survival vs disease progression or death. With this model, researchers used base-case and probabilistic sensitivity analyses to estimate the incremental cost-effectiveness and cost-utility ratios of the progression-free life-years and progression-free quality-adjusted life-years gained during 3-year and 5-year time horizons.

A willingness-to-pay threshold of $150,000 per progression-free quality-adjusted life-year determined the probability of a treatment being cost-effective in the probabilistic sensitivity analysis. The expected value of perfect or partial perfect information was calculated from the respective net health benefits and net monetary benefits.

Using these methods, they found that when compared with ibrutinib, acalabrutinib produced a 3-year incremental cost-effectiveness ratio (ICER) of $90,571 based on a probabilistic sensitivity analyses result of $88,588 per progression-free life-year gained. When compared with ibrutinib, zanubrutinib produced a 3-year ICER of $58,422 based on a probabilistic sensitivity analyses result of $58,907 per progression-free life-year gained.

Regarding incremental cost-utility ratios (ICURs) compared with ibrutinib, acalabrutinib produced a 3-year ICUR of $117,098 based on a probabilistic sensitivity analyses result of $110,063 per progression-free quality-adjusted life-year gained. Zanubrutinib produced a 3-year ICUR of $73,027 based on a probabilistic sensitivity analyses result of $73,73,634 per progression-free quality-adjusted life-year gained.

When compared with zanubrutinib, acalabrutinib produced a 3-year ICER of $144,633 based on a probabilistic sensitivity analyses result of $134,964 per progression-free life-year gained and an ICUR of $197,227 based on a probabilistic sensitivity analyses result of $166,109 per progression-free quality-adjusted life-year gained.

The expected value of perfect information per patient was a net health benefit of 0.036 progression-free quality-adjusted life-years and a net monetary benefit of $3,602 forgone, which produced an expected value of perfect information for the population as a whole of $134,766,957 forgone. 

For effectiveness, the expected values of partial perfect information per patient were a net health benefit of 0.015 progression-free quality-adjusted life-years (PFQALY) and a net monetary benefit of $1,479; the corresponding values for costs were 0.032 PFQALY and $3,187, and the corresponding values for health-related quality of life forgone were 0.015 PFQALY and $1,519.

“Additional evidence is needed to address the relative efficacy of the BTKis,” Dr Abraham and colleagues noted.