Which Treatments Are Linked with Favorable Outcomes in MDS?

Patients with myelodysplastic syndrome (MDS) plus DDX41 mutations appear to have favorable outcomes from allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) or when treated with venetoclax, according to research presented at the Eleventh Society of Hematologic Oncology Annual Meeting.

After retrospectively analyzing a large cohort of patients with MDS and DDX41 mutations,  presenter Alex Battaler, MD, PhD, and colleagues from the University of Texas MD Anderson Cancer Center, found median response rates as high as 85% and a two-year overall survival (OS) up to 100%, depending on the type of treatment.

“Response rates were high, and OS was improved in patients receiving venetoclax, although not statistically [significant],” the authors wrote.

They also reported that “outcomes appear favorable with [allogeneic HSCT].”

As responses and outcomes with specific therapies haven’t previously been investigated for MDS with DDX41 mutations, the researchers sought to retrospectively gather these data from 45 patients treated at their institution between 2010 and 2022. The patients had a median age of 70 and 80% were male; 69% had diploid cytogenics.

Based on the Revised International Prognostic Scoring System, 9% of patients were considered as very-high risk, 27% as high risk, 40% as intermediate risk, and 18% as low risk.

The researchers reported that 44% of the patients had no co-mutations besides DDX41. Among those with co-mutations, 18% had SXL1 mutations, 13% had TP53 mutations, and 9% had SRSF2 mutations. They also found that 91% had a germline DDX41 mutation and 39% had both a germline and somatic DDX41 mutation.

Of the previously untreated patients, 89% received treatment; 76% of these patients had low-intensity therapies (including low-dose chemotherapy or hypomethylating agents), 22% received low-intensity therapies with venetoclax, and 2% were given lenalidomide.

The patients who received low-intensity therapies had an 84% response rate, while those who received low-intensity therapies with venetoclax had an 85.1% response rate. These patients were followed up for a median of 52 months and had median OS of 70 months.

Notably, those who received venetoclax had a 100% two-year OS rate compared with 86.3% of those treated with venetoclax. However, that difference did not reach statistical significance (P= 0.34).

In other results, the researchers observed a 37% two-year cumulative incidence of progression or acute myeloid leukemia (AML) transformation for patients achieving response. Furthermore, 33% of patients received allogeneic HSCT and had a median two-year OS rate of 85% after allogeneic HSCT.

Reference

Bataller A, Loghavi S, Gerstein Y, et al. Characteristics and outcomes of patients with myelodysplastic syndrome and DDX41 mutation. Abstract MDS-208. Presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.