Disease Progression and Leukemic Transformation in Lower-Risk Myelofibrosis Patients

Progressive disease in myelofibrosis is associated with increased bone marrow fibrosis, worsening anemia, and increased circulating blasts. It can lead to leukemic transformation (LT), a rare but fatal complication. There are few real-world data regarding PD and LT in patients (pts) with low-risk MF. This analysis from the Myelofibrosis and Essential Thrombocythemia Observational Study (MOST; NCT02953704) describes the incidence of PD, including LT, in patients with lower-risk MF and compares the baseline characteristics of patients who developed PD with those who did not develop PD. MOST is a prospective, longitudinal, noninterventional study of patients with MF or essential thrombocythemia enrolled in clinical practices in the United States.

Patients (18 y) with low-risk or intermediate-1– (INT-1) risk MF (by age >65 y alone) stratified by the Dynamic International Prognostic Scoring System (Blood. 2010;115:1703) and followed for 3 y were eligible. As previously described (Gerds. CLML., 2022), baseline information was collected. PD was defined as physician-reported PD, LT, or death owing to PD during the study. Of the 232 patients with MF enrolled in MOST, 204 were analyzed (with PD, n=59; without PD, n=134; unknown, n=11; cutoff: September 30, 2022).

The median time from MF diagnosis to enrollment was 1.8 (range: 0-38) years; the median duration of registration was 4.4 (range: 3.5-5.6) years. Patients with PD were older than patients without PD, and a more significant proportion of Black versus White patients had PD. A lesser proportion of PD patients were employed (20.3% vs. 44.4%, P=0.0003), and a more significant proportion were unable to work (16.9% vs. 2.2%). Change in hematologic parameters (45.8%), changes in spleen size (32.2%), change in MF symptoms (27.1%), and change in blast counts (13.6%), LT occurrence (25.4%), and death due to PD (20%) were physician-reported indicators of PD in descending order of frequency among the 59 patients (28.9%) with PD. 

For low- versus INT-1-risk groups, the percentage of patients with a change in blast counts was higher (20% versus 10.3%), LToccurrence was lower (20% versus 28.2%), and mortality due to PD was lower (10% versus 25%). At enrollment, there were no statistically significant differences in symptomology between PD and non-PD patients. This real-world analysis of MOST describes the disease progression in MF patients with reduced risk. About one-third of pts had PD; pts with PD were elderly, less likely to be employed or able to work, and more likely to be Black than pts without PD. 

At enrollment, a more significant proportion of patients with PD were receiving RUX than HU, and patients receiving RUX were more likely to exhibit signs of progression (older age, splenomegaly, and prolonged disease duration), suggesting that RUX use was more prevalent among patients at greater risk for PD. Further longitudinal analyses from MOST will provide additional insight into PD risk factors to enhance disease management and outcomes for MF patients at lower risk.

Source: https://library.ehaweb.org/eha/2023/eha2023-congress/385495/rami.s.komrokji.disease.progression.and.leukemic.transformation.in.patients.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27888%2Atrend%3D4016%2Amarker%3D4178

Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02953704

Rami S. Komrokji,  Michael Grunwald,  Evan Braunstein,  J.E. Hamer-Maansson,  Tricia Kalafut,  John Mascarenhas/DISEASE PROGRESSION AND LEUKEMIC TRANSFORMATION IN PATIENTS WITH LOWER-RISK MYELOFIBROSIS: AN ANALYSIS FROM MOST/Inc, M. G. (n.d.). DISEASE PROGRESSION AND LEUKEMIC TRANSFORMATION IN PATIENTS WITH… by Rami S. Komrokji. Library.ehaweb.org. Retrieved July 18, 2023, from https://library.ehaweb.org/eha/2023/eha2023-congress/385495/rami.s.komrokji.disease.progression.and.leukemic.transformation.in.patients.html?f=menu%3D16%2Abrowseby%3D8%2Asortby%3D2%2Ace_id%3D2489%2Aot_id%3D27888%2Atrend%3D4016%2Amarker%3D4178