Cost-effectiveness of frontline blinatumomab in children with standard-risk B-cell acute lymphoblastic leukemia in Ontario, Canada Free

Introduction: The Children's Oncology Group trial AALL1731 (Gupta, NEJM 2025) investigated the addition of the bispecific T-cell engager blinatumomab to standard chemotherapy in children with newly diagnosed, standard-risk (SR: age 1-<10 years, white blood cell count <50,000/µL) B-cell acute lymphoblastic leukemia (ALL). Adding blinatumomab was associated with substantial improvements in disease-free survival (DFS), prompting its adoption as a new standard of care in most of North America. To date however, there is little data on the cost-effectiveness of frontline blinatumomab, limiting its reimbursement and uptake in many jurisdictions. We thus conducted a cost-effectiveness analysis of blinatumomab vs standard chemotherapy for this indication from a public health care payer perspective in Ontario, Canada.

Methods: We used a childhood ALL-specific microsimulation model (Pechlivanoglou, JNCI 2025) to simulate 30,000 children newly diagnosed with SR B-cell ALL and who met SR-Avg or SR-High criteria by AALL1731 risk stratification, based on multiple factors including minimal residual disease and leukemia cytogenetics. The cohort was assigned to receive chemotherapy with or without blinatumomab as frontline therapy and was observed over a lifetime horizon (maximum 90 years). Event probabilities and post-event trajectories for development of relapsed disease, receipt of bone marrow transplant (BMT), relapse post-BMT, and death were informed bya combination of DFS and overall survival (OS) estimates from the AALL1731 trial, real-world outcomes from Ontario administrative data, and published estimates of long-term mortality risk (Yeh, JAMA Onc 2020). We assumed the effect of frontline blinatumomab would wane by 10 years post-randomization (i.e., hazard ratio for PFS linearly returns to 1.0). All simulated patients in the frontline blinatumomab arm received two non-sequential cycles with 96-hour bags requiring an average of two inpatient days and seven outpatient visits per cycle. Costs for healthcare utilization and chemotherapy administration for both arms were sourced from Ontario administrative data, provincial formularies, and published sources (presented in 2024 Canadian [CAD] dollars). The cost of blinatumomab was assumed to be $2,978.26 CAD per 38.5mcg. ALL-specific quality of life estimates were sourced from published literature. Parameter uncertainty in cost-effectiveness outcomes (lifetime costs and quality-adjusted life years [QALY]) were propagated using Monte Carlo simulation and a probabilistic sensitivity analysis (n=500 iterations). The reference case assumed that patients who developed relapsed/refractory disease would receive blinatumomab as part of second-line therapy, regardless of whether blinatumomab was given as first-line, and with efficacy informed by the pivotal trial AALL1331 (Brown, JAMA 2021). An additional scenario analysis assumed no use of blinatumomab as part of second-line therapy.

Results: The simulated cohort (n=30,000) had an average age at diagnosis of 4.87 years (SD: 2.42), with 49.3% males, similar to the AALL1731 trial population. In the reference case, three-year DFS and OS rates for the blinatumomab arm were 95.4% and 97.6%, respectively, vs. 91.5% and 97.0% in the chemotherapy arm. Projected life expectancy in the blinatumomab arm was 68.4 years, compared to 66.5 years in those who received chemotherapy alone as frontline therapy. The addition of blinatumomab to standard chemotherapy resulted in 1.08 additional QALYs per patient and an additional cost of $31,741 CAD, resulting in an incremental cost-effectiveness ratio [ICER] of $29,281/QALY. Frontline blinatumomab was thus cost-effective at a willingness-to-pay threshold of $50,000 CAD with a probability of 87%. The scenario assuming no use of blinatumomab in relapse resulted in slightly lower costs and QALYs for both strategies, but the ICER remained largely stable at $29,039/QALYs.

Conclusions: Incorporating blinatumomab into first-line therapy for children with SR B-cell ALL is likely to yield improvements in life expectancy and quality of life but with added cost. Our results suggest however that blinatumomab for this indication would be considered cost-effective by most definitions. Its cost-effectiveness compares favorably to that of other recently adopted interventions in ALL and in oncology at large.