Prescribing patterns in MDS/MPN syndromes

Abstract Introduction: Myelodysplastic Syndrome (MDS)-Myeloproliferative Neoplasms (MPN) overlap syndromes, such as Chronic Myelomonocytic Leukemia (CMML), Atypical Chronic Myeloid Leukemia (aCML), Juvenile Myelomonocytic Leukemia (JMML) and Myeloproliferative Neoplasm- Unclassifiable (MPN-U) are a group of rare and diverse hematological disorders characterized by features of both dysplasia and overproduction. The treatment for these disorders ranges from supportive care to mutation specific therapy and even bone marrow transplant, but there is a lack of treatment guidelines for management of these syndromes. Given the high morbidity and mortality of MDS/MPN overlap syndromes and limited real-world data, we analyzed treatment patterns and outcomes in a contemporary cohort, comparing treated vs. untreated patients to potentially inform clinical practice. Methods: Data were obtained from TriNetX, a global federated research network providing access to de-identified electronic health records from participating healthcare organizations. We conducted a retrospective analysis using this large database, to analyze the treatment patterns in a cohort of patients with CMML, aCML, JMML or MPN-U. Additionally, the prescribing patterns of Hydroxyurea, Hypomethylating Agents (HMA)- Azacitidine/Decitabine and JAK inhibitors Ruxolitinib/Cedazuridine/Pacritinib/Momelotinib/Fedratinib were analyzed in these patients. All-cause mortality in this group was compared with that of individuals not receiving treatment. Results: Patients with CMML, atypical CML, JMML or MPN-U receiving treatment were identified. Only 219 (6.13%) patients received treatment for these conditions while 3,354 did not receive any of the treatments mentioned above. The mean follow up was 475.301 and 864.414 days respectively for treated vs untreated group. In the treatment group, the mean age at the index event was 70.3 years; 136 (63%) were male. The majority were White (n=171). In the treatment group, 109 patients died, with a median overall survival of 244 days (mortality risk: 50.7%). Prescribing patterns were as follows: Hydroxyurea (n=136, 61%), Azacitidine (n=41, 18.7%), Decitabine (n=31, 14.2%), and Ruxolitinib (n=13, 5.9%). Fewer than 10 patients received either Cedazuridine or Pacritinib, while no patients were treated with Momelotinib or Fedratinib. After propensity score matching, there were 216 patients in each cohort (treated vs untreated). Mortality was significantly higher among untreated patients (Hazard Ratio: 2.02; 95% CI: 1.48–2.75). There was no difference in mortality between those exclusively on hydroxyurea or those on HMAs. The outcomes between those getting exclusively HMA or JAK inhibitors could not be explored due to the small size of the cohorts. Conclusions: In this real-world analysis, our data demonstrate that over 90% of patients diagnosed with MDS/MPN overlap syndromes do not receive any treatment in routine clinical practice. The most prescribed medication in this cohort of patients with MDS/MPN was hydroxyurea, followed by hypomethylating medications (decitabine and azacitidine). Being untreated was associated with a significant decrement in survival, with untreated patients having up to twice the risk of death than those treated. Despite rapid scientific advances and growing evidence supporting the efficacy of novel agents such as JAK inhibitors in MDS/MPN overlap syndromes, real-world data reveal a striking gap: the vast majority of patients receive no treatment at all. This disconnect between innovation and implementation is concerning and underscores an urgent need to bridge the gap between scientific progress and patient care.