Prior to targeted therapies, allogeneic hematopoietic stem-cell transplantation (HSCT) was the primary therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) with del(17p). Treatment options now include oral ibrutinib, which produces significant progression-free survival (PFS) and overall survival (OS) with acceptable safety and the convenience of being noninvasive.1 However, complete remission is unlikely, and ibrutinib is not considered curative. HSCT has curative potential but is associated with high upfront cost, potential transplant-related morbidity and mortality, and potential relapse. Considering these different profiles, the authors presented a cost-effectiveness and cost-utility analyses of ibrutinib versus HSCT in R/R CLL del(17p) from a US payer perspective.2
Markov models (3-year and lifetime horizon) were constructed specifying 3 health states: PFS with embedded substates specifying whether the patient is on or off therapy, disease progression, and death. Historical data sources were used to simulate the R/R CLL del(17p) patients treated with ibrutinib3 or HSCT.4 In the 3-year Markov model, compared with HSCT, ibrutinib showed cost-savings of $48,642 (probabilistic sensitivity analyses [PSA], $48,678), incremental gains of 0.23 (PSA, 0.22) life-years (LYs) and 0.20 (PSA, 0.19) quality-adjusted life-years (QALYs), yielding an incremental cost-effectiveness ratio (ICER) of savings of –$211,487 (PSA, –$221,246) per LY gained and an incremental cost-utility ratio (ICUR) of savings of –$243,210 (PSA, –$256,200) per QALY gained. By contrast, in the lifetime Markov model, ibrutinib showed an incremental cost of $25,802 (PSA, $23,317), incremental gains of 0.12 (PSA, 0.09) LY and 0.13 (PSA, 0.11) QALY, yielding an ICER of $215,016 (PSA, $259,077) per LY gained and an ICUR of $198,476 (PSA, $211,972) per QALY gained.
The authors concluded that against a 3-year time horizon, ibrutinib prevails in OS and PFS over HSCT in the management of patients with del(17p) R/R CLL. As it is also cost-saving, ibrutinib has the 3-year benefit of being clinically superior in combined efficacy and safety at lower cost, but without curative potential. Against a lifetime horizon, ibrutinib still prevails in OS and PFS over HSCT but less so. It is no longer cost-saving as treatment costs continue, and attains cost-effectiveness at a willingness-to-pay threshold of approximately $260,000. Although the long-term curative potential of HSCT merits clinical consideration for young, fit patients, the lower survival probability in the first 3 years of treatment may be relevant for elderly and less fit patients. Ibrutinib provides significantly greater clinical and economic value over the first 3 years of treatment in patients with R/R CLL del(17p) versus HSCT, whereas the benefit declines beyond 3 years.
- Burger JA, et al. N Engl J Med. 2015;373:2425-2437.
- Alsaid N, et al. ASH 2017. Abstract 4679.
- O’Brien S, et al. Lancet Oncol. 2016;17:1409-1418.
- Schetelig J, et al. J Clin Oncol. 2008;26:5094-5100.