The Role Of Hypomethylating Agents

Hypomethylating agents (HMA) are a class of drugs that can reverse DNA and trigger it to reprogram tumor cells. They offer an effective treatment option for MDS and AML patients. Especially older, non-fit patients. “DNA hypomethylating drugs reprogram tumor cells to a normal-like state and sensitize the cells to chemotherapy and immunotherapy.”

Azacitidine and Decitabine

The first generation of HMAs are azacitidine and decitabine and they are routinely used to treat myeloid leukemias. A majority of cancer gene silencing is due to hypomethylating agents. 

• Azacitidine has been shown to increase a patient’s response rate by 60% and delay the progression of leukemia.
• Patients treated with azacitidine had a higher overall survival rate of 24.5 months.
• A clinical trial showed that patients treated with decitabine had a higher (17%) overall response.
• MDS patients treated with decitabine had increased survival compared to those treated with chemotherapy (22 months vs. 12 months).
• Decitabine has also been effectively used in older patients who do not qualify for standard chemotherapy.
• Azacitidine and decitabine are a mainstay treatment for high-risk MDS patients.

Hypomethylating agents are an eligible option for those who are not healthy enough for a stem cell transplant. They may also be used to decrease the number of blasts in the bone marrow and help normalize the blood cell levels.

Side Effects

HMAs can have side effects:

• Nausea and vomiting.
• Diarrhea or constipation.
• Weakness and fatigue.
• Blood cell levels may drop temporarily, which will require a blood transfusion.

Conclusion

HMAs are drugs that “are a type of chemotherapy that work by blocking the DNA that helps cancer cells grow. They also help genes that are involved in cell growth work the way they should. Using one of these drugs may help improve blood cell counts, which may lead to fewer blood transfusions and improve quality of life.”

Hypomethylating agents are considered a non-intensive treatment. They aim to slow the progression of the disease with as few side effects as possible. They will not cure MDS, but they can alter its composition.

Typical treatment regimen:

• decitabine (20 mg/m² per day for five days at 4-week intervals) 
• azacitidine (75 mg/m² per day for seven days at 4-week intervals) for at least six cycles