OBJECTIVES: Ibrutinib, acalabrutinib, and zanubrutinib are BTKis approved for CLL treatment. This study evaluated clinical benefits and associated treatment-related costs of BTKis using data from package inserts, clinical trials, and real-world evidence (RWE).

METHODS: A semi-Markov simulation model estimated clinical outcomes and costs of BTKi treatment for 1L and R/R CLL, incorporating treatment-related care during progression-free and post-progression periods, overall survival, safety, and tolerability data, from the US Medicare perspective. Treatment-related costs (reported as per treated patient per month [PTPPM]) included costs associated with routine maintenance and clinical care; adverse event (AE)-related costs were reported over 1-year/5-year time horizons (TH). AE PTPPM costs were applied over a 1-year TH due to inconsistent reporting at longer time points. Scenario analyses examined the impact of ibrutinib dose reduction (DR).

RESULTS: Among modeled patients with 1L CLL, average total life years over 1-year/5-year TH for ibrutinib, acalabrutinib, and zanubrutinib were 0.99/4.80, 0.99/4.68, and 0.99/4.65, respectively; for R/R CLL those numbers were 0.96/4.08, 0.96/4.16, and 0.97/4.35, respectively. Discounted treatment-related costs PTPPM were $48/$64, $46/$58, and $46/$60 for 1L CLL, and $87/$96, $90/$108, and $86/$93 for R/R CLL; AE PTPPM costs were $520, $457, and $489 for 1L CLL and $740, $706, and $570 for R/R CLL, respectively. Ibrutinib DR resulted in a 17.2% drop in AE PTPPM costs among patients with ibrutinib-treated 1L CLL and among patients with R/R CLL.

CONCLUSIONS: Using base case assumptions and conservative clinical efficacy estimates, these findings suggest similar clinical benefits and costs across BTKis in 1L CLL. Clinical benefits and treatment-related costs were also similar among patients with R/R CLL, and AE PTPPM costs were similar after accounting for potential DRs. Scenario analyses using recently published RWE and clinical trial data also support the comparable value of ibrutinib relative to other BTKis.