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.
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 |