PROJECTED IMPACT OF PERSONALIZED MRNA NEOANTIGEN VACCINES ON MELANOMA RECURRENCE IN MEDICARE BENEFICIARIES: A PARAMETRIC SURVIVAL AND THRESHOLD COST-EFFECTIVENESS ANALYSIS
Author(s)
Marjan Zakeri, MD, PhD1, Yijia Sun, MS1, Samuel Wagner, MPharm, PhD2, Nehir Yapar3, Onur Baser, PhD4.
1Columbia Data Analytics, New York, NY, USA, 2Columbia Data Analytics, Newtown, PA, USA, 3Director of Data Science, Columbia Data Analytics, New York, NY, USA, 4City University of New York (CUNY), New York, NY, USA.
1Columbia Data Analytics, New York, NY, USA, 2Columbia Data Analytics, Newtown, PA, USA, 3Director of Data Science, Columbia Data Analytics, New York, NY, USA, 4City University of New York (CUNY), New York, NY, USA.
OBJECTIVES: To estimate recurrences averted and assess cost-effectiveness thresholds for intismeran autogene plus pembrolizumab in Medicare-eligible patients with high-risk resected melanoma, using a Weibull parametric survival model anchored to 5-year KEYNOTE-942 trial data.
METHODS: A Weibull proportional-hazards model was fitted to 4 published recurrence-free survival (RFS) landmark estimates from KEYNOTE-942 (12, 18, 30, and 60 months). All-cause mortality was overlaid using US Center for Disease Control and Prevention (CDC) 2022 national life tables, assuming a cohort starting age of 70 years. Net survival was defined as the product of Weibull RFS and all-cause mortality survival. The primary outcome was 3-year cumulative recurrences averted, applied to 15,000 annually eligible Medicare beneficiaries at 50% uptake. A threshold cost-effectiveness analysis estimated the maximum vaccine cost consistent with cost-effectiveness at willingness-to-pay (WTP) thresholds of $100,000-$200,000/QALY, using utility weights from KEYNOTE-054 EQ-5D data and recurrence costs from Medicare claims literature. Sensitivity analyses varied uptake (30%-70%), hazard ratio across the KEYNOTE-942 (95% CI, 0.294-0.887), recurrence cost ($100k-$250k), and WTP threshold.
RESULTS: The Weibull model provided good fit (R²=0.894 and 0.845 for combination and monotherapy arms). At 50% uptake, 1,303 recurrences were averted and 30,016 recurrence-free life-months gained over a 3-year horizon. All-cause mortality adjustment reduced projected recurrences averted by 6.4% versus an unadjusted estimate. At a WTP of $150,000/QALY, the maximum cost-effective vaccine price was $33,878 per treated patient, with 77% of the break-even price driven by recurrence cost offsets ($26,060/patient) rather than QALY gains. Sensitivity analyses projected 161-2,810 recurrences averted and $23,000-$54,000 maximum cost per patient.
CONCLUSIONS: Personalized mRNA neoantigen vaccination could avert 1,303 recurrences annually among Medicare-eligible patients with high-risk resected melanoma. The threshold cost-effectiveness analysis provides a trial-anchored economic benchmark to inform payer coverage deliberations ahead of regulatory approval.
METHODS: A Weibull proportional-hazards model was fitted to 4 published recurrence-free survival (RFS) landmark estimates from KEYNOTE-942 (12, 18, 30, and 60 months). All-cause mortality was overlaid using US Center for Disease Control and Prevention (CDC) 2022 national life tables, assuming a cohort starting age of 70 years. Net survival was defined as the product of Weibull RFS and all-cause mortality survival. The primary outcome was 3-year cumulative recurrences averted, applied to 15,000 annually eligible Medicare beneficiaries at 50% uptake. A threshold cost-effectiveness analysis estimated the maximum vaccine cost consistent with cost-effectiveness at willingness-to-pay (WTP) thresholds of $100,000-$200,000/QALY, using utility weights from KEYNOTE-054 EQ-5D data and recurrence costs from Medicare claims literature. Sensitivity analyses varied uptake (30%-70%), hazard ratio across the KEYNOTE-942 (95% CI, 0.294-0.887), recurrence cost ($100k-$250k), and WTP threshold.
RESULTS: The Weibull model provided good fit (R²=0.894 and 0.845 for combination and monotherapy arms). At 50% uptake, 1,303 recurrences were averted and 30,016 recurrence-free life-months gained over a 3-year horizon. All-cause mortality adjustment reduced projected recurrences averted by 6.4% versus an unadjusted estimate. At a WTP of $150,000/QALY, the maximum cost-effective vaccine price was $33,878 per treated patient, with 77% of the break-even price driven by recurrence cost offsets ($26,060/patient) rather than QALY gains. Sensitivity analyses projected 161-2,810 recurrences averted and $23,000-$54,000 maximum cost per patient.
CONCLUSIONS: Personalized mRNA neoantigen vaccination could avert 1,303 recurrences annually among Medicare-eligible patients with high-risk resected melanoma. The threshold cost-effectiveness analysis provides a trial-anchored economic benchmark to inform payer coverage deliberations ahead of regulatory approval.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
CO28
Topic
Clinical Outcomes, Health Policy & Regulatory, Health Service Delivery & Process of Care
Disease
Oncology, Vaccines