Response rates to hypomethylating agent (HMA) therapy were similar between higher-risk myelodysplastic syndromes (MDS) with or without IDH1 mutations; however, IDH1-mutated patients showed poor median overall survival (OS) when they did not receive an IDH1 inhibitor.
These conclusions were derived from a retrospective analysis presented at the Society of Hematologic Oncology 2024 Annual Meeting by Ziad Abuhelwa, MD, MPH, of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida.
According to the report, patients with higher-risk MDS show poor outcomes after failing HMA therapy with a median OS between four and six months. The authors noted the IDH1 inhibitor ivosidenib had recently been approved for relapsed or refractory IHD1-mutated MDS after it yielded a median OS of three years in a small cohort study.
The analysis included 1,057 patients with MDS, the majority of which (>90%) were categorized as higher-risk by International Prognostic Scoring System-Molecular score. The authors reported IDH1 mutations in 32 (3%) patients, with R132C being the most common mutation in 50%.
Upfront HMAs included azacitidine (61.5%), decitabine (14.4%), oral decitabine (1.5%), HMA plus venetoclax (11.1%), and other HMA combinations (11.5%). The complete response rate to HMA therapy was comparable between IDH1-mutated and non-mutated patients at 16% and 14%, respectively (P=.78).
After HMA failure, the median OS was 9.6 months for mutated patients and 10.3 months for non-mutated patients. Notably, four patients received an IDH1 inhibitor (ivosidenib or olutasidenib) after HMA failure and showed a significantly improved median OS of 28.6 months compared with 5.1 months in those who did not receive an IDH1 inhibitor.
“IDH1 inhibitors significantly improve survival in IDH1-mutated patients in real world data,” Dr. Abuhelwa and colleagues suggested.
Reference
Abuhelwa Z, Al Ali N, Xie Z, et al. Outcome after hypomethylating agents failure in patients with IDH1 mutated myelodysplastic syndromes. Abstract #MDS-290. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.