Study shows indicators of venetoclax response in therapy-related myeloid neoplasm

Blood cancers

By Mardi Chapman

13 Jan 2022

Dr Mithun Shah

Venetoclax can induce deep remission in a subset of patients with aggressive therapy-related myeloid neoplasm (t-MN), according to research conducted at the Mayo Clinic and the Central Adelaide Health Network.

A retrospective review of 367 WHO-defined cases of t-MN was presented at the 63rd ASH Annual Meeting and Exposition.

The Mayo’s Dr Mithun Shah told the meeting that 24.5% of patients received a venetoclax-based regimen.

Those who received venetoclax were more likely than other patients to have therapy-related AML, abnormalities of chromosome 17, complex karyotype or monosomal karyotype and were therefore a higher risk group.

He said overall 43.4% of patients achieved complete remission (CR).

“However upon continuation, a majority – that is 78.3% – has progressive disease at the last follow-up,” he said.

“The likelihood of achieving CR was lower in: those with chromosome 7 abnormality, prior hypomethylating agent use, the use of venetoclax for progressive disease as opposed to newly diagnosed disease, and the use of chemotherapy backbone other than a hypomethylating agent.”

He said the likelihood of achieving CR was no different based on the % blasts at the time of venetoclax initiation.

Dr Shah said the median PFS from starting venetoclax was 4.9 months and median OS was 7.6 months.

Again, median PFS and OS did not differ when stratified by % blasts at diagnosis or % bone marrow blasts (≥20% vs <20%) at the initiation of venetoclax.

Predictors of poor PFS were: the presence of a chromosome 7 abnormality, the absence of prior radiation and the presence of a pathogenic variant in RUNX1.

“Similarly, improved OS was noted when using HMA backbone, achieving MRD-negative CR, or using venetoclax for newly diagnosed disease as opposed to progressive disease.”

Australian co-authors on the abstract included Professor Andrew Wei and Dr Ing Soo Tiong from the Alfred Hospital in Victoria, and Dr Devendra Hiwase and Dr Rakchha Chhetri from SAHMRI, Adelaide.

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