ABSTRACT
Introduction
Acute myeloid leukemia (AML) predominantly affects elderly population. This poses challenges in management, as patients are frequently not candidates for intensive therapy given comorbidities or frailty. Currently, azacitidine (AZA), either as monotherapy or in combination regimens, is the backbone treatment in this group of patients.
Areas covered
We review the mechanism of action, pharmacology, clinical efficacy, and safety of AZA. It reviews current combination therapies of AZA with other targeted therapies for the treatment of newly diagnosed AML.
Expert opinion
AZA is a cornerstone for the treatment of patients considered ineligible for intensive chemotherapy induction, but better results and therapies are required for these patients. AZA has shown synergistic properties when combined with other medications. Its safety profile and few drug interactions make it a suitable medication to use as backbone. Newer therapies are being combined with AZA, demonstrating safety and in cases, improved responses, and survival. AZA/venetoclax has emerged as the standard of care for patients who are ineligible for intensive chemotherapy. Doublet and triplet combinations are increasingly being studied. With the results observed in elderly patients, the intensive chemotherapy paradigm might be put to test in younger populations, with AZA combinations being at the forefront.
Abbrivations
2HG – 2-hydroxyglutatate
Allo-SCT – allogeneic stem cell transplant
AML – Acute myeloid leukemia
AZA – Azacitidine
BCL-2 – B-cell lymphoma 2
BSC – best supportive care
CMML – chronic myelomonocytic leukemia
CR – complete remission
CRc – composite complete response
CRi – complete remission with incomplete hematologic recovery
CYP3A – cytochrome P450, family 3, subfamily A
CYP450 – cytochrome P450
DFS – disease-free survival
DNA – deoxyribonucleic acid
ECOG – eastern cooperative oncology group
EFS – event-free survival
EHA – European Hematology Association
EMA – European Medicines agency
FAB – French American British
FDA – the US food and drug administration
FL – FLT3 ligand
FLT-3 – FMS-like tyrosine kinase 3
HMA – hypomethylating agent
HR – hazard ratio
IDH1 – Isocitrate dehydrogenase 1
IDH2 – Isocitrate dehydrogenase 2
IPSS – International prognostic scoring system
ITD – Internal tandem duplication
ITT – Intention to treat
JM – Juxtamembrane
LDAC – low-dose ara-C
MDS – myelodysplastic syndrome
mOS – median overall survival
NCCN – national comprehensive cancer network
ORR – overall response rate
OS – Overall survival
R/R – relapsed/refractory
RFS – relapse-free survival
RNA – ribonucleic acid
SC – subcutaneous
TKD – tyrosine kinase domain
WHO – world health organization
αKG – alpha ketoglutarate
Declaration of Interest
The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.