Economic evaluation of ponatinib vs reference and generic imatinib in front-line management of philadelphia chromosome-positive acute lymphoblastic leukemia: A value dilemma.

BACKGROUND Acute lymphoblastic leukemia (ALL) mainly affects children, though it also occurs in adults. About 25% of adults with ALL have the more aggressive Philadelphia chromosome-positive (Ph+) subtype. Standard treatment includes tyrosine kinase inhibitors (TKIs) in combination with chemotherapy or corticosteroids, which have greatly enhanced survival rates over the past 2 decades. Ponatinib, a third-generation TKI demonstrated greater efficacy compared with imatinib, a first-generation TKI, in the PhALLCON trial.

OBJECTIVE To conduct an economic evaluation of ponatinib compared with (1) reference imatinib, (2) the average cost of several imatinib generics, and (3) the weighted cost of imatinib in adults with Ph+ ALL from the US payer perspective.

METHODS Cost-effectiveness and cost-utility analyses were performed using a partitioned survival model with 3 mutually exclusive health states: progression-free, progressed disease, and death. A time horizon of 60 months and a 3% discount rate were applied. The incremental costs per 1% gain in probability of progression-free survival and overall survival at 60 months were estimated.

RESULTS Life-years (LYs) and quality-adjusted LYs (QALYs) were higher for ponatinib (3.74, 2.15) than for imatinib (3.52, 1.68). Compared with reference imatinib, ponatinib was dominant, having cost savings of $56,024. Compared with average generic imatinib, ponatinib had an incremental cost of $147,147, yielding an incremental cost-effectiveness ratio (ICER) of $668,150 per LY gained and incremental cost-utility ratio (ICUR) of $314,646 per QALY gained. Compared with weighted imatinib, ponatinib had an incremental cost of $128,861, yielding ICER of $585,122 per LY gained and ICUR of $275,546 per QALY gained. The differential cost of ponatinib per patient for a 1% increase in the probability of remaining in the progression-free survival state was $6,883 in savings compared with reference imatinib, but an additional $18,077 compared with average generic imatinib and $15,835 compared with weighted imatinib.

CONCLUSIONS Ponatinib demonstrated cost savings relative to reference imatinib, though its incremental costs were substantially higher when compared with both average and weighted imatinib, for an approximate gain of 3 months of life and 6 months of quality-adjusted life. This presents a value dilemma: whether to save money with more affordable alternatives for a slightly lower clinical benefit, possibly parlaying these cost-efficiencies into expanded patient access. This highlights the challenge of balancing clinical benefits with economic sustainability, particularly when the modest health gains come at a substantially higher cost. Although ponatinib offers therapeutic value, payers and policymakers must carefully evaluate whether the clinical outcomes justify the additional costs, considering also its safety profile.