External validation of the Molecular International Prognostic Scoring System (IPSS-M) for myelodysplastic syndromes

7056 Background: Myelodysplastic Syndromes (MDS) comprise of a group of clonal diseases characterized by dysplastic hematopoietic progenitor cells, leading to cytopenias and in select cases transformation to acute myeloid leukemia (AML). In June 2022 the Molecular International Prognostic Scoring System (IPSS-M) was developed to build on the traditional IPSS-R and is reported to be prognostic even with incomplete molecular data. We aimed to validate this scoring system with an external dataset, and utilize a patient population which typically does not contain complete molecular testing at diagnosis. Methods: This single center study at a tertiary medical center in New York, NY was conducted as an external validation of the IPSS-M. Patients with MDS who had documented peripheral blood counts, bone marrow biopsies, and cytogenetic data were identified in the institutional tissue bank. After eliminating repetitive patient samples, 405 patient entries, collected between July 7, 2010 and March 29, 2022 were included in this study. 392 patients had previously been categorized by IPSS-R score. 332 patients had at least one subsequent follow-up event. 94 patients had bone marrow biopsies that were peri-diagnostic (within 12 months of diagnosis). Results: Patients in the entire cohort had a median age of 74 years (range, 30-96). The median follow-up duration was 1.5 years (range 0.0-9.9 years). Nearly all patients had at least partial molecular diagnostic data. Other than PRPF8 mutations (0%), all other mutations included in the IPSS-M scoring system were tested in a subset of the study population. The most common mutations in the patient population were SF3B1 (20.4%), ASXL1 (17.6%), and SRSF2 (15.9%); 12.2% of patients had the del5q cytogenetic abnormality, and 5.6% were found to have at least one TP53 mutation; 2.7% were TP53 (multi-hit). 29% of all patients were up-staged from IPSS-R to IPSS-M score, while 12% were down-staged. At the time of study evaluation, there were 84 events; 61.3% of patients were alive at the time of analysis. The median overall survival was 3.6 years (25-75% range: 2.75-5.50 years). When limited to patients with peri-diagnostic bone marrow biopsies, there were statistically significant differences in overall survival between IPSS-M categories (p<0.000001) as well as IPSS-R categories (p<0.00001). There was no statistical difference in survival between IPSS-M categories (p=0.6) or IPSS-R categories (p = 0.2) if scores were calculated at any time point in the patient’s disease course. Conclusions: This study validates the utility of both the IPSS-M and the IPSS-R scoring systems, and notably retains important risk stratification with incomplete diagnostic data. Importantly, the scoring systems are not effectively prognostic as the disease progresses, and thus should only be utilized at or near the time of diagnosis.