A study led by Shai Shimony, MD, Dana-Farber, revealed the significant impact of molecular ontogeny classification on outcomes among newly diagnosed acute myeloid leukemia patients treated with hypomethylating agents (HMA) +/- venetoclax (VEN).
A previous study from our institution demonstrated that molecular ontogeny classification into three groups, correlates with survival in patients treated with intensive induction chemotherapy. In A L, we wondered if this ontogeny classification also implies in patients treated with hypomethylating agents. And the novel BC L two inhibitor venetoclax, which is considered today the standard of care for older patients or patients with multiple comorbidities. We found that the adversaries of secondary ontogeny does not apply in patients with AM L treated with hypomethylating agents plus Veneto clocks. The this is due to the marked benefit seen with Veneto clocks added to H MA that doubles the survival time and equalizes the survival to that of the novo patients. In stark contrast, we saw that in T 53 ontogeny, similar dismal outcomes were seen whether patients were treated with Veneto clocks or without Veneto clocks added to their hypomethylating agents suggesting that the addition of Veneto only adds cost and potential toxicity. Our findings support the re evaluation of secondary ontogeny as adverse risk prognosis in AM L treated with hypomethylating agents plus Veneto clocks and challenge the utility of using Veneto clocks in T 53 mutated AM L.
