Dr Daver on Persisting Gaps in the Treatment of Relapsed/Refractory Higher-Risk MDS

“MDS is, in general, a very unmet need. We have not had any major change in the treatment of frontline, high-risk MDS beyond single-agent, hypomethylating agents. There have been many efforts, but if we can finally develop a combination, this will at least hopefully improve response rates, allow more patients to go to transplant, and hopefully have a longer and better curative outcome.”

Naval G. Daver, MD, a professor and director of the Leukemia Research Alliance Program in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, discussed persisting gaps in the treatment of patients with relapsed/refractory higher-risk myelodysplastic syndromes (MDS). Despite the widespread use of hypomethylating agents (HMAs) such as azacitidine (Vidaza) and decitabine (Dacogen) as frontline therapy, outcomes remain suboptimal, and the majority of patients eventually relapse, he began. No major therapeutic advances have emerged beyond single-agent HMAs, underscoring the urgent need for novel strategies, Daver said.

During his discussion, Daver emphasized that while investigational combinations with HMAs have shown promise, including HMA plus venetoclax (Venclexta) regimens currently being evaluated in the phase 3 VERONA trial (NCT04401748), effective standard-of-care options remain lacking. Following HMA failure, patients face extremely poor prognoses, with limited alternatives outside of palliative approaches such as hydroxyurea, low-dose cytarabine, or supportive care. He noted that this represents one of the most pressing unmet needs in hematologic malignancies.

From a disease biology standpoint, Daver explained that new agents capable of modifying the disease course, improving response durability, and potentially extending overall survival are critically needed. Beyond disease control, novel therapies may expand the proportion of patients eligible for allogeneic stem cell transplantation, offering the possibility of long-term remission or cure. He noted that treatment goals differ between transplant-ineligible patients—where durable disease control remains the focus—and transplant-eligible patients, where deeper responses may allow more patients to successfully proceed to transplant.

Looking ahead, Daver highlighted the importance of integrating novel biologic and immune-based agents into the MDS treatment paradigm. He emphasized that the development of effective options for patients who relapse after HMAs would represent a major advance, not only by improving outcomes but also by providing a therapeutic bridge for those at high risk of progression.

Daver concluded that relapsed/refractory higher-risk MDS continues to be defined by limited treatment options and poor outcomes after HMA failure. Ongoing efforts to develop novel agents and rational combinations are essential to improve survival, expand transplant opportunities, and address this significant area of unmet need.