Pharmacoeconomic considerations for acute myeloid leukemia pharmacotherapy

ABSTRACT

Introduction

Acute myeloid leukemia (AML) is a rare blood cancer with a poor prognosis. Recently, targeted drugs have improved survival both in the elderly and in fit patients. However, as monthly costs of targeted agents are high, regulatory bodies often impose restrictions on their use.

Areas Covered

The authors review the value-for-cost of targeted drugs such as gemtuzumab ozogamycin, CPX-351, midostaurin, gilteritinib, glasdegib, venetoclax, oral azacytidine and enasidenib used to treat adult AML. EMBASE and TRIP databases, together with authority websites were searched for technology assessments. Add-on drugs, namely midostaurin and gemtuzumab ozogamycin, have been reported to have the best pharmacoeconomic profile for newly diagnosed fit patients with FLT3 mutation or favorable/intermediate cytogenetics, since allogeneic transplant rates were stable or reduced. Most of the other drugs, on the other hand, did not achieve highly favorable cost-for-benefit, due to a poor absolute survival gain and/or increased transplant rates.

Expert opinion

The cost of most targeted therapies for AML in unfit patients seems unfair in comparison to the absolute survival advantage provided in fit patients. Point of cure and transplant outcomes should be standardized to allow comparability among the models.

KEYWORDS:

• Acute myeloid leukemia
• azacitidine
• venetoclax
• gilteritinib
• glasdegib
• enasidenib
• CPX-351
• cost-effectiveness
• gemtuzumab ozogamycin

Highlights box

• Acute myeloid leukemia (AML) is a rare, life-threatening blood cancer that includes several clinical entities characterized by specific molecular features. Recently approved targeted drugs, as well as enhanced chemotherapy formulations, have improved survival in specific patient populations.

• Although AML has a low impact on health-care budget – except for allogeneic transplants and hospitalizations, novel agents might significantly increase the costs of care.

• FLT3 inhibitors and gemtuzumab ozogamicin proved to be cost-effective for fit patients (with FLT3 mutation or a favorable/intermediate cytogenetics) receiving intensive chemotherapy, since the rate of allogeneic transplants was found to remain stable or decrease.

• Targeted therapies for unfit patients, such as venetoclax and glasdegib, achieved less satisfactory cost-effectiveness, as the level of absolute survival benefit was found to be low.

• Liposomal formulations of daunorubicin and cytarabine have improved survival of AML patients with myelodysplasia-related changes and therapy-related AML at high incremental cost, as toxicity was reported and an enhanced amount of patients achieved allogeneic stem cell transplantation.

• Although their pharmacoeconomic profile should be further investigated, oral maintenance therapies, such as oral azacitidine, seem promising opportunities for those patients not receiving transplant.

• Personalized innovative therapies of AML are expected to improve clinical outcomes, but they might not achieve a favorable cost-effectiveness as compared with current standards of care, unless prices are adjusted to the benefit-for-cost of the drug.

• Standardization of pharmacoeconomic models for AML is hastened in order to assess the results and compare the profile of different novel treatment strategies. In particular, time horizon, point of cure, and post-transplant outcomes are features to be shared.

List of abbreviations

LDAC low-dose cytarabine

AZA azacitidine

ICUR incremental cost-utility ratio

HR hazard ratio

CAD Canadian dollars

USD United States Dollars

AML acute myeloid leukemia

FLT3 Fms-like tyrosine kinase 3

IDH isocitrate dehydrogenase

SCT stem cell transplantation

CPX-351 liposomal daunorubicine cytarabine

QALY quality-adjusted life years

US United States

MDS myelodysplastic syndrome

OS overall survival

PFS progression-free survival

FDA Federal and Drug Administration

EMA European Medicines Agency

HAS Haute Autorité de Santé

G-BA Gemeinsamer Bundesausschuss

pCODR pan-Canadian Oncology Drug Review

PBAC Pharmaceutical Benefits Advisory Committee

NICE National Institute for Clinical Excellence

SMC Scottish Medicines Consortium

PAS Patient Access Scheme

IC intensive chemotherapy

BSC Best Supportive Care

ASCO American Society of Clinical Oncology

ASH American Society of Hematology

EHA European Hematology Association

ISPOR International Society of Pharmacoeconomic and Outcome Research

PDGFR Platelet Derived Growth factor Receptor

HDAC Hystone DeAcetylase

MDM2 Mouse Double Minute 2 homolog

ASMR amelioration du service medical rendu (improvement of the medical service provided)

Acknowledgments

The authors thank Samantha Farinelli, a literary translator, who helped to revise the manuscript

Declaration of Interest

M Marchetti has received consultancy fees from Celgene and Gilead Sciences as well as speaker’s fees from Amgen Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.