Real-world analysis of a large electronic medical record database of patients with higher-risk myelodysplastic syndromes (HR MDS): Treatment profiles, clinical effectiveness, and key adverse events

Patients (pts) diagnosed with HR MDS are predominantly older (median age ≈70 years), with severe comorbidities and poor performance status, and often experience suboptimal outcomes with currently available therapies. In recent years, approved treatment options have remained limited; therefore, more effective therapies with tolerable safety profiles are needed to improve prognosis. This lack of evidence has prompted the evaluation of real-world evidence to understand and establish the level of baseline care and current unmet needs in pts with HR MDS.

This descriptive, retrospective cohort study used structured electronic medical record data from ConcertAI’s RWD360 database, which consists of pts from a large network of community and academic oncology practices who are representative of the US population. The data set spanned from Jan 1, 2010, to Oct 21, 2022. Pts with HR MDS were indexed into treatment-based cohorts upon treatment initiation (hypomethylating agents as monotherapy [HMAs], immunosuppressive therapy [IST], venetoclax ± HMAs [VEN], lenalidomide [LEN], hematopoietic stem cell transplant [HSCT], and supportive care only [including luspatercept, epoetin alfa, and/or darbepoetin alfa]). Outcomes assessed over follow-up (index date to censoring date) included overall survival (OS), time to acute myeloid leukemia (AML) transformation, incident anemia, thromboembolic events, cardiac events, and infections.

A total of 2028 pts with HR MDS (median follow-up, 258 days) were identified from an overall MDS cohort (N=36,424), including 1052 treatment-naive pts. The median age of all pts with HR MDS was 70 years (IQR, 62-77 years), with a majority of male pts (59.1%). HMAs were the most used approved therapy in this pt population (59%), while 10% of pts received VEN off-label. Most pts in each treatment cohort except for HSCT and IST received care in the community setting. Pts who received HSCT were the youngest (median age, 60 years), followed by VEN (69 years), HMAs (72 years), IST (73 years), and LEN (75 years), with the oldest pts mainly receiving supportive care (80 years). Over 80% of pts in the overall HR MDS cohort developed anemia, ≈14% had cardiac arrhythmia, ≈7% had cardiac failure, and >20% had an infection over the follow-up period (Table). Overall, 75% of pts died during the follow-up period (median OS, 296 days). The median OS observed in the HSCT cohort was over twice that of the overall cohort; the shortest median OS was in the supportive care cohort (Table). During the follow-up period, >40% of pts in the HR MDS cohort transformed to AML (≈30% each in the HMA, IST, and HSCT cohorts; 47% in the VEN cohort). The estimated median time to AML transformation in the overall HR MDS cohort was 346 days (95% CI, 302-403 days), with the shortest time occurring in the VEN cohort; the median was not reached in the HSCT and supportive care cohorts (Table).

These results provide key insights into establishing a baseline of clinical effectiveness of currently available therapies for HR MDS in the real world. Investigation into differences between treatment cohorts in survival (eg, longer in HSCT than in others) and time to AML transformation (eg, shorter in VEN than in others) is warranted as these may be due to underlying pt characteristics and/or clinical risk profiles that require further assessment.