Cost-Effectiveness Of Midostaurin In The Treatment Of Acute Myeloid Leukemia With The FLT3 Mutation In Spain

Abstract

Purpose

The addition of midostaurin to standard chemotherapy (cytarabine and daunorubicin) has shown significant improvements in the survival of patients with acute myeloid leukemia with the FLT3 mutation (FLT3-AML). The objective of this study was to determine whether this intervention would be cost-effective in Spain.

Methods

A partitioned survival model with five health states was developed (diagnosis and induction, complete remission, no complete remission, transplantation and death). A lifetime time horizon and the Spanish National Health System perspective were adopted. During the first three years, permanence in the different health states was determined according to the results of the RATIFY study. In successive years, the death rates of the Spanish population adjusted by a factor to reflect long-term disease-related mortality were used. Utilities were obtained from the literature. Pharmacological costs (first and second line) and the costs of other health resources (hospitalizations, visits and tests) were included. The robustness of the model was evaluated by deterministic and probabilistic sensitivity analyses.

Results

The addition of midostaurin resulted in 1.46 life years gained (LYG) and 1.23 quality-adjusted life years (QALY) gained and implied an additional cost of € 47,955, resulting in an incremental cost-effectiveness ratio (ICER) of € 32,854/LYG and an incremental cost-utility ratio of € 38,985/QALY. In the univariate sensitivity analysis, the threshold of € 50,000/QALY was not exceeded in any case; taking into consideration potential discounts of 20-40% in the PVL of midostaurin the ICER would be below € 30,000/QALY, a commonly accepted threshold in Spain. In the probabilistic analysis, when the threshold was € 50,000/QALY, midostaurin was cost-effective in 82.3% of simulations.

Conclusion

According to our modeling, midostaurin, in combination with standard chemotherapy, could be an efficient alternative for the treatment of FLT3-AML in Spain.

Keywords:

• AML
• modeling
• efficiency
• health economics
• economic evaluation

Acknowledgments

The authors of the manuscript wish to thank Dr. Elena Amutio for his participation in the panel of experts who validated the model inputs and assumptions, and Gabriel Tremblay for his support during the performance of the sensitivity analyses.

Abbreviations

AE, adverse event; AML, acute myeloid leukemia; CADTH, Canadian Agency for Drugs and Technologies in Health; CGCOF, Consejo General de Colegios Oficiales de Farmacéuticos; CI, confidence interval; CMBD, Conjunto Mínimo Básico de Datos; CMV, cytomegalovirus; CR, complete remission; DRG, diagnosis-related group; FLAG-IDA, fludarabine, cytarabine, idarubicin; FLT3, FMS-like tyrosine kinase 3; GPE, generic pharmaceutical equivalent; GVHD, graft versus host disease; HAS, Haute Autorité de Santé; HR, hazard ratio; HSCT, hematopoietic stem cell transplantation; ICER, incremental cost-effectiveness ratio; ICU, intensive care unit; ICUR, incremental cost-utility ratio; LYG, life year gained; MEC, mitoxantrone, etoposide, cytarabine; NICE, National Institute for Health and Care Excellence; PVL, ex-factory price; QALY, quality-adjusted life year; RDL, royal decree law; VZV, varicella-zoster virus; WHO, World Health Organization.

Author Contributions

Each author of the present work affirms that:

• They have participated substantially in the work (conception and design of the study, or acquisition, analysis, and interpretation of data) taking public responsibility for the content of the paper and has critically revised and approved the final version of the manuscript.

• Agree to be accountable for all aspects of the study, ensuring that questions related to the accuracy or integrity of any part of the study are appropriately investigated and resolved.

• If requested, the authors will provide the data or will cooperate fully in obtaining and providing the data on which the manuscript is based for examination by the editors or their assignees.

Disclosure

AA, RD, JE, CM, JS and JLV are, respectively, employed by San Carlos Hospital, University Hospital of Getafe, Clinic Hospital of Barcelona, University Hospital of Araba, Hospital Santa Creu i Sant Pau and Hospital Sant Joan de Déu. JS reports grants and personal fees from Novartis and personal fees from Daiichi Sankyo, during the conduct of the study and grants and personal fees from Novartis, outside the submitted work. CM reports non-financial support from Novartis, outside the submitted work. JML is employed by Hospital 12 de Octubre, CNIO and Complutense University and reports grants and personal fees from Novartis, Janssen, Bms, and Incyte, during the conduct of the study. PM is employed by University Hospital La Fe and CIBERONC - Instituto Carlos III. DML and AMF are employees of Oblikue Consulting, an independent contract health economic organization that received consultancy fees from Novartis Farmacéutica, S.A. to conduct this research. AMF reports grants from Oblikue Consulting, during the conduct of the study. RDN and JG are employees of Novartis Farmacéutica, S.A., the marketing authorization holder for Rydapt^® (midostaurin). The funding body was not involved in the study design, collection and interpretation of the data, or the decision to publish. The authors report no other conflicts of interest in this work.