AML World Awareness Day | Current therapies and treatments 

Acute myeloid leukemia (AML) is a malignant cancer characterized by the infiltration of bone marrow by proliferative, abnormally differentiated, heterogeneous, clonal hematopoietic stem cells (HSCs), leading to bone marrow failure, and ultimately death if untreated.¹

These abnormal white blood cells progressively occupy the bone marrow niche, where healthy HSCs ordinarily reside and are maintained.² Emerging evidence suggests that leukemic cells induce molecular changes in hematopoietic cells, contributing to the transformation of the normal bone marrow niche into a ‘leukemia’ niche, allowing the growth and proliferation of leukemic cells, disrupting the ordinary functioning of HSCs.³

To classify the disease, morphological assessments are carried out on bone marrow and the blood is analyzed for the expression of cytoplasmic markers using flow cytometry.⁴ Major categories of AML include therapy-related AML, AML with myelodysplasia-related changes, AML with recurrent genetic abnormalities and AML otherwise not specified.⁵

Current therapies include induction therapy, consolidation therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), with those ineligible for intensive therapy receiving supportive care, low-dose cytarabine and the hypomethylating agents, azacitidine and decitabine. Targeted therapy drugs have also been introduced in recent years, with a ficus on FLT3 and IDH inhibitors.

The AML Global Portal has reported on drugs that have recently been approved, or are in the process of being approved:

• FDA grants ivosidenib Breakthrough Therapy Designation
• Regulatory review granted by EMA for gilteritinib
• FDA approves gilteritinib to treat relapsed or refractory AML with FLT3 mutation
• FDA grants venetoclax approval to treat newly diagnosed AML
• NICE recommends gemtuzumab ozogamicin for patients with untreated CD33+ AML

Over the last year, the AML Global Portal has reported on drug approvals around the world:

April 2018

• 23 April: European Commission grants approval for gemtuzumab ozogamicin for previously untreated CD33-positive AML

May 2018

• 23 May: Australian Department of Health approves midostaurin to treat newly diagnosed FLT3+ AML patients

July 2018

• 20 July: FDA grants approval for the treatment of patients with relapsed/refractory IDH1 AML

August 2018

• 27 August: European Commission approves CPX-351 for the treatment of therapy-related AML

November 2018

• 21 November: FDA approves glasdegib to treat newly diagnosed AML patients ineligible for intensive chemotherapy
• 21 November: FDA grants approval for venetoclax to treat patients newly diagnosed with AML
• 28 November: FDA approves gilteritinib to treat relapsed/refractory FLT3+ AML patients

Despite the development of optimal therapeutic approaches, such as intensive chemotherapy and allogeneic HSC transplantation, only a minority of patients are cured successfully. Thus, designing and developing more effective therapeutic approaches, that target key molecular mechanisms driving pathogenesis, to improve clinical outcomes is desirable.

Please visit www.know-aml.com for more information about AML World Awareness Day.