Venetoclax is considered a breakthrough treatment for acute myeloid leukemia (AML). But venetoclax combination therapies do not seem to be as useful for treating acute myeloid leukemia that develops as a complication of myeloproliferative neoplasms, a condition known as post-MPN-AML, according to a study recently published in Blood Advances.

Post-MPN-AML is rare, but it has what researchers call a “dismal prognosis,” so effective therapies to help patients survive and be eligible for stem cell transplantation (SCT) are urgently needed. And while venetoclax, a B-cell lymphoma inhibitor, may seem to hold promise, it also may be responsible for too many adverse events to be an optimal choice.

The researchers analyzed 31 patients: 14 newly diagnosed and 17 relapsed/refractory, making this the largest analysis of safety and efficacy of venetoclax strategies (VEN-b) of post-MPN-AML patients from 1 center (in this case, the University of Texas MD Anderson Cancer Center). With one exception, all the patients went through a short ramp-up period until they were receiving 400 mg daily.

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When they evaluated the patients’ response to the treatment, the researchers found the marrow remission in the newly diagnosed, or frontline (FL), patients was 43%, with a median overall survival of 7 months. But none of the relapsed/refractory patients achieved remission, and their median overall survival was 3 months.

“Observed responses in FL patients were comparable to those described with already available regimens … and more importantly did not translate into improved survival or greater ability to undergo SCT, the ultimate goal for all eligible patients,” the researchers wrote.

The researchers also found that 83% of the patients experienced a grade 3 or higher infections such as pneumonia, bacteremia, or sepsis during the initial cycle. Then, 85% of the 20 patients who received subsequent cycles of VEN-b therapy experienced grade 3 or higher infections. This kind of severe infectious complication in the majority of patients makes this approach “challenging for clinical practice,” they noted.

The study is limited by its nature as a retrospective analysis, the researchers acknowledged. But they maintained that although patients with post-MPN-AML are among the most difficult to treat subgroups of AML, more research is needed to find a treatment with the potential to “elicit disease response while maintaining acceptable safety and allow eligible patients to undergo potentially curative SCT.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Masarova L, DiNardo CD, Bose P, et al. Single-center experience with venetoclax combinations in patients with newly diagnosed and relapsed AML evolving from MPNs. Blood Adv. 2021;5(8):2156-2164. doi:10.1182/bloodadvances.2020003934