Dr. Nazha on Mutational Model to Predict Response to Hypomethylating Agents in MDS

Aziz Nazha, MD
Published: Wednesday, Oct 07, 2015



Aziz Nazha, MD, hematologist, Leukemia Program at the Cleveland Clinic, Taussig Cancer Institute, discusses results of a mutational model to predict response to hypomethylating agents in myelodysplastic syndromes (MDS).

In a recent study, 122 patients with MDS and myeloid malignancies treated at the Taussig Cancer Institute between 2000 and 2012 received four cycles of azacitidine or decitabine. Using a gene mutation panel, patients were then divided into those who had complete responses, partial responses, or hematologic improvements, and those who demonstrated no response, Nazha explains. Certain mutations, such as IDH1 and IDH2, were found to be most prevalent among those who responded, as well as TET2 and RAD21. However, patients with ASXL1 were less likely to respond to these treatments.

A multi-variant analysis used these data to determine important prognostic factors that impact response in patients with MDS. In a new mutational model, patients who harbor the IDH1, IDH2, or TET2 mutation have a score of 1, while patients with STAG2 or RAD21 have a score of 2. For patients with the ASXL1 mutation, the score is –1.5. If a patient’s score is 2 to 3, the response rate for hypomethylating agents is 85%. If a score is –1.5, the response rate is 15% to 18%, Nazha says.

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Aziz Nazha, MD, hematologist, Leukemia Program at the Cleveland Clinic, Taussig Cancer Institute, discusses results of a mutational model to predict response to hypomethylating agents in myelodysplastic syndromes (MDS).

In a recent study, 122 patients with MDS and myeloid malignancies treated at the Taussig Cancer Institute between 2000 and 2012 received four cycles of azacitidine or decitabine. Using a gene mutation panel, patients were then divided into those who had complete responses, partial responses, or hematologic improvements, and those who demonstrated no response, Nazha explains. Certain mutations, such as IDH1 and IDH2, were found to be most prevalent among those who responded, as well as TET2 and RAD21. However, patients with ASXL1 were less likely to respond to these treatments.

A multi-variant analysis used these data to determine important prognostic factors that impact response in patients with MDS. In a new mutational model, patients who harbor the IDH1, IDH2, or TET2 mutation have a score of 1, while patients with STAG2 or RAD21 have a score of 2. For patients with the ASXL1 mutation, the score is –1.5. If a patient’s score is 2 to 3, the response rate for hypomethylating agents is 85%. If a score is –1.5, the response rate is 15% to 18%, Nazha says.




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