Lower-Risk Myelofibrosis Population Has High Disease Progression Rate

News
Article

The rate of disease progression among patients with low- or intermediate-risk myelofibrosis appeared to increase over time in the MOST study.

The median time to meeting criteria for first and second disease progression in cohort A was approximately 2 years for each (24.9 vs 28.2 months), whereas it was approximately 1 year (11.6 months) for reaching the third progression criteria.

The median time to meeting criteria for first and second disease progression in cohort A was approximately 2 years for each (24.9 vs 28.2 months), whereas it was approximately 1 year (11.6 months) for reaching the third progression criteria.

Disease progression occurred in a majority of patients with low- or intermediate-risk myelofibrosis, according to data from the prospective MOST study (NCT02953704) presented as a poster at the 2024 European Hematology Association (EHA) Congress.

A total of 232 patients with MF were enrolled, with 205 patients considered low or INT-1 risk due to being aged over 65 years alone comprising cohort A and 27 patients considered low or INT-1 risk for factors other than age only being evaluated in cohort B. In cohort A, 58.5% (n = 120) of patients experienced disease progression during the study, with the most common progression criteria being hemoglobin below 10 g/dL (47.5%). Further, 12 patients (10.0%) died due to disease progression and 6 (5%) had leukemic transformation. In cohort B, 29.6% (n = 8) of patients had disease progression during the course of the study.

Laboratory-defined criteria for progression in the MOST study included hemoglobin below 10 g/dL, platelet count below 100 × 109/L, less than 1% blasts, white blood cell count above 25 × 109/L, and leukemic transformation with greater than 20% blasts. Physician-reported criteria for progression were constitutional symptoms (weight loss, fever, sweats), new or worsening splenomegaly, 1 red blood cell transfusion during the study, physician-reported leukemic transformation, and death due to disease progression. The presence of at least 1 criterion was considered disease progression.

Other progression criteria met in cohort A included a platelet count below 10 × 109/L in 31.7%, constitutional symptoms in 30.8%, and splenomegaly in 28.3%. Hemoglobin below 10 g/dL was present in 21 of 29 patients (72.4%) of those who had 3 or more progression criteria.

Importantly, the rate of progression appeared to increase over the course of the study. The median time to meeting criteria for first and second disease progression in cohort A was approximately 2 years for each (24.9 vs 28.2 months), whereas it was approximately 1 year (11.6 months) for reaching the third progression criteria.

Looking at patients with vs without progression during the study, in cohort A, more patients were over 65 at the time of diagnosis (53.3% vs 35.3%, P =.0384). However, the median time from diagnosis to enrollment was similar between the groups, with a median of 1.9 vs 1.4 years (P = .9997). There was also not a significant difference in the median duration of enrollment for patients in cohort A with or without disease progression (4.5 vs 4.3 years). Most patients in cohort A were receiving MF-directed therapy at the time of enrollment regardless of whether they experienced disease progression (59.2% vs 61.2%); however, more patients with progression were receiving ruxolitinib (Jakafi; 59.2% vs 14.1%, P = .0078), and fewer patients with progression were receiving hydroxyurea (22.5% vs 36.5%, P = .0913). In cohort B, the median time from diagnosis to enrollment was 1.9 years (range, 0-31), and the median duration of enrollment was 4.3 years (range, 3.6-5.4).

Of all patients enrolled in both cohorts, 186 were tested for at least 1 known driver mutation. In cohort A, 108 of 158 had a JAK2 mutation, and 66 of 93 patients had disease progression whereas 42 of 65 without progression had the JAK2 mutation. Of those evaluated for CALR mutation, 33 of 44 had a mutation with 16 of the 21 with disease progression having it and 17 of the 23 without progression having the mutation present. Five out of 31 had an MPL mutation, with 1 out of 6 having the mutation among those who experienced disease progression and 2 of 10 having it among those who did not experience disease progression.

Reference

Grunwald M, Gerds A, Agrawal A, et al. High rate of disease progression in patients with low-risk myelofibrosis (MF) enrolled in the prospective MOST study. Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P1053.

Recent Videos
Data from the phase 3 DeLLphi-304 trial at ASCO 2025 revealed a survival advantage with tarlatamab vs chemotherapy in second-line ES-SCLC.
The FDA approval of tarlatamab in SCLC has received much press attention, according to Daniel R. Carrizosa, MD, MS.
The National ICE-T Conference may inspire future collaboration between community and academic oncologists in the management of different cancers.
One of the largest obstacles to tackle in the kidney cancer landscape will be translating the research on rare kidney cancer subtypes into clinical trials.
Long-term toxicities like infections and secondary primary malignancies remain a concern when sequencing novel agents for those with multiple myeloma.
Zanzalitinib exhibited favorable data when evaluated alone or in combination with anti-PD-1 immune checkpoint inhibition in phase 1 RCC trials.
The investigational agent exhibited superior efficacy vs pembrolizumab in patients with lung cancer, suggesting potential efficacy in kidney cancer.
Management of adverse effects and access to cellular therapies among community oncologists represented key points of discussion in multiple myeloma.
“As a community, if we’re looking to help enroll and advocate for patients with rare [kidney cancers], we need to be aware of what is out there,” said A. Ari Hakimi, MD.
Treatment with the dual inhibitor displayed a short half-life and a manageable toxicity profile in patients with clear cell renal cell carcinoma.
Related Content