Work

P748: Ipss-m Performance in Patients With Myelodysplastic Syndrome at the Time of Hypomethylating Agent Failure

Year: 2023

Type: article

Abstract: Background: The international prognostic scoring system (IPSS) for prognostication of outcomes in myelodysplastic syndrome (MDS) has been widely adopted. The IPSS-Molecular was recently developed to aggregate the value of specific genetic mutations, as these have shown to have an impact on prognosis. Aims: This study seeks to evaluate the performance of IPSS-M in MDS the setting of hypomethylating agent (HMA) failure. Methods: We reviewed patients diagnosed with MDS who progressed after HMA therapy in a single institution. Clinical, laboratory, cytogenetic, and molecular data was collected and annotated. IPSS-M was calculated and models calculating overall survival were created using the Kaplan-Meier survivor function. The c-index was calculated to evaluate for model predictive performance. Results: We identified 101 patients of which most were male (66%) with a median age of 72 years (IQR: 41-88). Median blast percentage was 4% (IQR: 0-18), 30% had complex karyotype, and the most frequent mutations were TP53 (19%), ASXL1 (14%), TET2 (14%), RUNX1 (13%), DNMT3A (10%), and SF3B1 (10%). Twenty-nine percent were treated with azacitidine, 26% with decitabine, 12% with HMA with immunotherapy combinations (12%), azacitidine + anti-CD47 therapy (5%) SGI-110 (8%), ASTX727 (7%), or azacitidine with venetoclax (4%), or decitabine with venetoclax (1%). All others (8%) were treated with HMA in combination with other agents. IPSS-M categories were 34%, 28%, 15%, 12%, 9%, and 1% for Very High, High, Moderate-High, Moderate-Low, and Very -Low, respectively. The c-index for this model was 0.62 (log-rank p=0.08). Summary/Conclusion: This study documents that IPSS-M is not accurate at risk stratifying patients with MDS at the time of HMA failure. Despite the inclusion of molecular variables and patient stratification, the risk of death may be too high to be adequately captured.Figure 1. Kaplan-Meier survival function for overall survival of patients with HMA failure by IPSS-M categories with p-value for log-rank test. Keywords: International prognostic index, Myeloid malignancies, Myelodysplastic syndrome, Hypomethylating agents

Source: HemaSphere

DOI: 10.1097/01.hs9.0000969896.23789.ce