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Disease Progression for Patients With Low-Risk Myelofibrosis Participating in the MOST Study
A group of researchers presented data on disease progression for patients with low-risk myelofibrosis (MF) participating in the prospective observational Myelofibrosis and Essential Thrombocythemia Observational Study (MOST) at the 2023 ASH Annual Meeting & Exposition.
In order to qualify for the MOST study, participants were required to have a physician-reported diagnosis of MF (primary myelofibrosis [PMF], post progression of polycythemia vera [post-PV], or post essential thrombocythemia [post-ET). They also could not have any risk factors per the Dynamic International Prognostic Scoring System (DIPSS) criteria. However, participants could be aged 65 years or older. The number of patients with MF enrolled in the study was 232. Of this population, 205 met the study criteria and were included in cohort A. Although the remaining 27 patients had ≥1 DIPSS risk factor, they were included in the study in a separate cohort B.
For the study, disease progression was defined by the worsening of clinical or laboratory parameters, which included one or more of the following criteria: hemoglobin (Hb) <10 g/dL, platelets <100×109/L, presence of constitutional symptoms (weight loss, fever, or sweats), new or worsening splenomegaly, blasts >1%, white blood cell count >25×109/L, death due to disease progression, leukemic transformation (LT), or >1 red blood cell transfusion. The median follow-up was 52.9 months (42-68).
During the study, 120 (58.5%) patients in Cohort A had evidence of disease progression. Although baseline characteristics between patients with vs without disease progression were similar, those who progressed were older at diagnosis (median [range] 65.9 [21-88] years old vs 62.9 [35-86] years old) and at enrollment (median [range] 70.5 [35-88] years old vs 66.0 [35-88] years old). They also had a longer median (range) time from diagnosis to enrollment at 1.9 (0-38) years vs 1.4 (0-24) years. In addition, the percentage of patients receiving MF-directed therapy at enrollment was similar between the two groups (59.2% vs 61.2%), with the most common treatments being ruxolitinib (33.3% vs 14.1%) and hydroxyurea (22.5% vs 36.5%).
Among the patients in cohort A, 66 (71%) with disease progression and 42 (64.6%) without disease progression tested positive for JAK2 mutations. Of those tested for CALR mutations, 16 (76.2%) with disease progression and 17 (73.9%) without tested positive. Within the patients who had disease progression, 64 (53.3%) met one criteria, 27 (22.5%) met two criteria, and 29 (24.2%) met ≥3 criteria. The most common criteria met was Hb <10 g/dL at 47.5%. This was followed by platelets <100×109/L at 31.7%, constitutional symptoms at 30.8%, and new/worsening splenomegaly at 28.3%. Of the patients whose disease progressed, 6 (5.0%) developed leukemic transformation (LT) and 12 (10%) died due to progression.
In Cohort B at time of enrollment, 25 patients (92.6%) met one progression criteria. The most common criteria met was Hb <10 g/dL (13 patients [48.1%]). This was followed by 7 (25.9%) patients with a white blood cell count of >25×109/L, constitutional symptoms in 4 (14.8%) patients, and blasts >1% in 1 (3.7%) patient. One patient (3.7%) met 2 progression criteria (Hb <10 g/dL and constitutional symptoms), and one pt (3.7%) met 3 progression criteria (blasts >1%, constitutional symptoms, and white blood cell count >25×109/L). In addition, within Cohort B, 8 patients (29.6%) had evidence of further disease progression while participating in the study.
According to the authors, this is the first prospective analysis of disease progression in low-risk myelofibrosis, based on the MOST study. Overall, they found that over 4 years of follow-up, nearly 60% of patients with low-risk MF had evidence of disease progression, and 17 patients (8.3%) developed LT or died (both occurred in one patient). In addition, the results revealed a slow but increasing rate of progression over the course of the study for patients with low-risk MF.
Source: Grunwald MR, Gerds AT, Agrawal A, et al. High rate of disease progression in patients with low-risk myelofibrosis (MF) enrolled in the prospective, real-world MOST study. Presented at: 2023 ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA, and virtual; Abstract 3803.
