The role of decitabine in

MDS & AML

 Myelodysplastic syndromes (MDS)

Are heterogeneous malignant hematopoietic stem cell disorders characterized

by ineffective hematopoiesis, cytopenias, abnormal cellular maturation with
dysplastic features, and variable risk for progression to acute myeloid leukemia
(AML).
• Some patients with MDS have a change, or mutation in the JAK2 gene while
other patients will have mutation in certain chromosomes.
• MDS used to be classified as a pre-leukemia disease, but now that it has
been learned about, MDS is considered a type of blood cancer.
 Epidemiology of myelodysplastic syndromes

• Myelodysplastic syndromes/neoplasms (MDS) are seen mostly in older adults, but the
precise incidence is not well-defined.
• The annual incidence of MDS is approximately 4 per 100,000 people, according to the
United States Surveillance, Epidemiology, and End Results database. The median age at
presentation is 76 years and the risk of developing MDS increases with age. Disease onset
before age 50 is unusual. Rare cases of MDS are reported in children. There is a male
predominance in most categories of MDS.
MDS Treatment

Therapeutic options for MDS include:

• Supportive care
• Low-intensity therapy (including hypomethylating agents eg. Decitabine)
• High-intensity therapy (including allogeneic hematopoietic cell transplantation (HCT)
 Acute Myeloid Leukemia AML

Acute myeloid leukemia (AML) comprises a heterogeneous group of aggressive blood cell
cancers that arise from clonal expansion of malignant hematopoietic precursor cells in the
bone marrow. The leukemic cells interfere with production of normal blood cells, causing
weakness, infection, bleeding, and other symptoms and complications.
Epidemiology

AML is the second most common category of leukemia in adults and the most
common type of acute leukemia. Nevertheless, AML is relatively rare and it
accounts for approximately 1 percent of adult cancers in the United States, but

nearly 2 percent of cancer-related deaths.

AML treatment

The usual treatment of AML is divided into two phases:

• Induction of remission
• Post-remission therapy
Lower intensity therapy

• Lower intensity therapy — For patients who are unable to tolerate intensive
remission induction therapy, lower intensity therapies may control the
disease, prolong survival, and lessen symptoms.
• Lower intensity therapies include targeted agents for patients with specific
mutations, hypomethylating agents.
• One of the preferred options of treatment of Lower intensity therapies
include decitabine.
 Decitabine

• Is a member of class called Hypomethylating Agents (HMA), those agents

responsible for regulating the gene expression in the cells.
• It inhibits DNA methyltransferase, causing hypomethylation of DNA & cellular
differentiation or apoptosis.
 Decitabine indications

MDS AML

Primary and secondary MDS Primary AML

Previously treated and untreated MDS Secondary AML
Decitabine dosing

Decitabine Total
IV Dose and Schedule
Regimen Dose/Course

15 mg/m2 over 3 hrs every 8 hrs x 3

FDA Approved 135 mg/m2
days every 6 weeks

20 mg/m2 over 1 hr daily x 5 days

Active Alternative 100 mg/m2
every 4 weeks
Decitabine improves outcomes in older patients with acute
myeloid leukemia and higher blast counts
Tapan M Kadia 1, Xavier G Thomas 2, Anna Dmoszynska 3, Agnieszka Wierzbowska 4, Mark Minden 5,
Christopher Arthur 6, Jacques Delaunay 7, Farhad Ravandi 1, Hagop Kantarjian 1
DACO-016

Multicentre, randomised, open-label Phase 3 trial:

n=485 who met the inclusion criteria:

• ≥65 years
• Newly diagnosed de novo or secondary AML
• Poor or intermediate risk cytogenetics
• ECOG PS 0–2
DACO-016: conclusions

• This study was one of the largest randomised, controlled Phase 3 trials to date in
older patients with newly diagnosed AML
• Results indicated that in these difficult-to-treat older patients:
• Decitabine achieved a higher response rate, with a possible survival advantage,
compared with low-dose cytarabine or supportive care
• Decitabine was well tolerated vs treatment choice (cytarabine or supportive care)
• Results were consistent with those from Phase 2 DACO-017 study
Why Decitabine is important for the Patients?

• It has manageable adverse events.

• Improve their life quality.
• Single agent therapy.
• Convenient for the patients (either in-out hospital).
• Lack of other options in managing their disease.
• Available in all Iraqi centers.
What Decitabine can offer to the Physicians ?

• It’s considered as essential tool for treating MDS not only an option.
• It Have a manageable AEs & convenient for patients.
• It’s not a supportive therapy nor Highly intensive chemotherapy.
• There are an urgent need for HMA not only for the MDS but AML patients as well.
• achieve hematological improvement and prolong overall survival.
• It’s can alter the whole nature of the disease
Thank you