Navigating HMA-Venetoclax Duration of Response in MDS/MPN

In an interview with Targeted Oncology, David Sallman, MD, of Moffitt Cancer Center, addresses the nuanced decision-making surrounding hypomethylating agent (HMA)-venetoclax (Venclexta) therapy in myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN), particularly regarding treatment duration and patient selection. He emphasizes that the approach depends critically on whether a patient is a transplant candidate.

For patients with excess blast MDS and AML who are transplant-eligible, Sallman prioritizes clinical trials as the preferred option, given that standard-of-care outcomes remain "extremely poor." If a trial is unavailable, he adds venetoclax to HMA therapy because it achieves faster blast reduction and higher response rates. However, he cautions that response durations are "very, very short"— many patients relapse within 2 to 6 months — necessitating an expedited path to transplant.

Regarding venetoclax dosing, Dr Sallman uses a 21-day schedule during cycle one for transplant-eligible patients, performing a bone marrow biopsy at day 21 to assess response. Once a response is achieved, he rapidly reduces venetoclax to 14 days in cycle two and often to seven days in subsequent cycles. He notes that the VERONA trial (NCT04401748) established 14 days as a safe dose for MDS patients with less than 20% blasts, though he awaits results from the ongoing B-AML trial comparing 14-day versus continuous dosing before making broader practice changes.

For patients who are not transplant candidates, Dr Sallman favors single-agent HMA therapy — with a slight preference for oral decitabine for convenience —arguing that the combination adds toxicity without clear durability benefit. He also mentions an investigational metronomic regimen using low-dose decitabine with once-weekly venetoclax but strongly advises against community adoption until randomized trial data are available.