Non-intensive acute myeloid leukemia therapies for older patients

ABSTRACT

Introduction

Acute myeloid leukemia (AML) is an aggressive disease predominantly affecting the elderly population. The elderly population represents a challenging group to treat and the prognosis is generally poor with significantly worse treatment outcomes compared to the younger population. While the goal of treatment for younger fit patients is cure and includes intensive chemotherapy and stem cell transplantation, these strategies are not always feasible for elderly unfit patients due to increased frailty, co-morbidities, and, subsequently, an increased risk of treatment-related toxicity and mortality.

Areas covered

This review will discuss both patient- and disease-related factors, outline prognostication models and summarize current treatment options, including intensive and less intensive treatment strategies and novel agents.

Expert opinion

Although recent years have seen major advances in the development of low-intensity therapies, there is still a lack of consensus on the optimal treatment for this patient group. Because of the heterogeneity of the disease, personalizing the treatment strategy is important and curative-oriented approaches should be selected wisely, rather than following a rigid hierarchical algorithm.

KEYWORDS:

• Acute myeloid leukemia
• elderly population
• treatment options
• low-intensity therapy
• targeted therapy
• hypomethylating agents

Article highlights

• Older patients with AML constitute a proportionally large subgroup that is difficult to treat

• The use of venetoclax and other targeted agents like IDH and FLT3 inhibitors as monotherapy or low-intensity combination have significantly improved the outcomes

• Often the biological and chronological age of the patients are very dyssynchronous and precise models to assess patient fitness, tolerability to therapy and risks of initial treatment mortality are required to choose the right therapy intensity for an individual patient

• Older AML patients are better treated at high-volume AML centers

• More research is needed in order to understand which patient population will benefit from curative approaches, and who will benefit from moderate treatment or even supportive care.

Declaration of interest

F Ravandi receives honoraria, research funds, and/or consulting fees from Astellas, Astra Zeneca, Xenocor, Prelude, Abbvie, Novartis, Syos, Amgen, Celgene/BMS, and Astex/Taiho. 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 disclosres

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

Abbreviations

AML	=	Acute Myeloid Leukemia
BCL-2	=	B-cell lymphoma 2
BSC	=	Best supportive care
CCR	=	Conventional Care Regimen
CD	=	Cluster Designation
CR	=	Complete remission
DFS	=	Disease Free Survival
ECOG	=	Eastern Cooperative Oncology Group
EFS	=	Event free survival
GLI	=	Glioma associated oncogene homolog
GO	=	Gemtuzumab Ozogamicin
HCT-CI	=	Hematopoietic stem cell transplantation comorbidity index
HH	=	Hedgehog
HMA	=	Hypomethylating agents
HSCT	=	Hematopoietic Stem Cell Transplantation
IDH	=	Isocitrate Dehydrogenase
mAbs	=	Monoclonal Antibodies
MDR1	=	Multidrug resistance 1
MDS	=	Myelodysplastic Syndrome
MRD	=	Minimal residual disease
ORR	=	Overall response rate
OS	=	Overall Survival
QoL	=	Quality of Life
RFS	=	Relapse Free Survival
sAML	=	Secondary AML
TRM	=	Treatment-related mortality

Additional information

Funding

This paper was not funded.