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Importance of NGS and Targetable Mutations Stressed in AML

Angelica Welch
Published: Wednesday, Aug 15, 2018

Suman Kambhampati, MD
Suman Kambhampati, MD
There are many molecular subgroups in acute myeloid leukemia (AML) that reflect the evolution of the disease and aid in prognostication, according to Suman Kambhampati, MD. In recent years, certain mutations have provided clues as to how to optimally treat patients.

-ITD, and new agents on the horizon for the treatment of patients with AML.

Impact of NGS

One of the most discussed AML abstracts at the 2018 ASCO Annual Meeting, according to Kambhampati, investigated the impact of NGS on treatment selection for patients with AML.1 This retrospective analysis looked at NGS of more than 1400 patients who were treated over a decade, beginning with a 53-gene panel, and followed by a 28-gene panel.

, as they have associated targeted therapies.

BCL-2 Inhibitors

AML cells have a high expression of BCL-2, said Kambhampati. Investigators are looking at combining venetoclax (Venclexta) with either decitabine or azacitidine in elderly patients with AML (NCT02203773).

Inclusion criteria for this study include an age of 65 years or older, ineligibility for standard induction therapy with cytarabine and anthracycline, and an ECOG performance status of 0 to 2. Key exclusion criteria include prior hypomethylating agents or chemotherapy for antecedent hematologic disorder, chimeric antigen receptor T-cell therapy, active central nervous system involvement, white blood count >25 x 109 per liter, and infection with HIV, or hepatitis B or C.

Overall, venetoclax plus either decitabine or azacitidine demonstrated a tolerable safety profile. Investigators confirmed preliminary data which suggested that 400 mg of venetoclax is the optimal dose in this combination. Kambhampati said that early responses were promising across high-risk subgroups, such as those with poor cytogenetics, secondary AML, and aged 75 years and older.2

Kambhampati said that treating patients who have poor cytogenetics has traditionally been challenging as they struggle with chemotherapy. Best supportive care for these patients is the last resort after failure on demethylating therapies.

“With a median 15.6 months of follow up, the observed median overall survival (OS) was 17.5 months, with approximately 50% survival at 1 year,” said Kambhampati. “Pretty remarkable results compared with what we are used to with best supportive care and/or demethylating therapies.”

Additionally, minimal residual disease was achieved in more than 45% of patients treated with the 400 mg dose of venetoclax plus azacitidine.

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