Myelofibrosis
Myelofibrosis (MF) is a rare blood cancer that leads to scarring in the bone marrow, which prevents the normal production of blood cells. The condition is a primary subtype of myeloproliferative neoplasms (MPNs) and, in some cases, starts as another MPN. Risk factors for primary MF are unclear, although a history of polycythemia vera (PV) or essential thrombocythemia (ET) are risk factors for development of secondary MF. The disease is stratified as low, intermediate, or high risk using various International Prognostic Scoring System scales, and the prognosis depends on individual risk factors including age, comorbidities, and treatment response.
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New therapies, such as TP-3654, are currently being explored in combination studies.
Three of four patients with myelofibrosis had objective responses at one year, and no dose-limiting toxicities were observed.
No significant differences in HSCT were observed, suggesting haploidentical HSCT as an acceptable treatment approach.
AI-driven quantitative analysis was compared with manual evaluation of bone marrow trephine slides in a phase II trial.
Julie Braish, MBBCh, discusses her study on JAK2 allele burden in myelofibrosis presented at ASCO 2024.
Dr. Rampal, of Memorial Sloan Kettering Cancer Center, discusses his abstract at the EHA 2024 Congress in Madrid, Spain.
MPN depend on mutated JAK signaling, and targeting the mutations suppressed disease features and improved overall survival.
Pelabresib plus ruxolitinib improved spleen and symptom responses in JAKi-naïve patients with myelofibrosis.
Treatment with luspatercept improved transfusion burden and anemia across four cohorts of patients with myelofibrosis.
Prefibrotic PMF is an MPN with distinct characteristics comprising histopathological, clinical, and biological parameters.
Prefibrotic myelofibrosis is the focus of “SOHO State of the Art Updates and Next Questions.”
Momelotinib achieved higher rates of transfusion independence compared with ruxolitinib.
Splenic irradiation before HSCT is associated with reduced spleen size and lower incidence of relapse in patients with MF.
Sotatercept monotherapy, and combined with ruxolitinib, is a safe and effective treatment for patients with PMF and anemia.
The primary endpoint was overall best response after blast-reduction therapy.
Momelotinib and ruxolitinib improved bone marrow fibrosis, but changes were not associated with improved outcomes in MF.
Nicolaus Kröger, MD, discusses a study on GVHD and its impact on relapse in patients with myelofibrosis undergoing HSCT.
Myelofibrosis, a rare blood cancer, affects four to six per 100,000 individuals in the United States.
An international working group collaborating with the EBMT and ELN updated the 2015 guidelines for HSCT in myelofibrosis.
Ruxolitinib plus pelabresib was well tolerated and improved spleen and symptom burden in patients with myelofibrosis.
Parsaclisib plus ruxolitinib can improve symptoms and spleen volume in certain patients with myelofibrosis.
FREEDOM2 is a phase III study comparing fedratinib with best available therapy as a second-line treatment for myelofibrosis.
“Among the high-risk splicing mutations, SRSF2 has the worst prognostic role,” Dr. Braish and colleagues wrote.
The REVEAL study identified five risk factors, including leukocytosis, duration of time with PV, and more.
The treatment led to reduced hepcidin levels when used alone or in combination with ruxolitinib.
Venugopal highlights myelofibrosis research at ASH 2023.
Dr. Al-Ali covers data on combined BET and JAK inhibition for patients with myelofibrosis presented at the 2023 ASH Meeting.
SRSF2 and SF3B1 were the most common splicing mutations, followed by U2AF1 and ZRSR2.
CALR and MPL mutations, which are associated with better outcomes, showed earlier mutation clearance than JAK2.
Mass spectrometry–based proteomics were used to learn more about how MKs drive bone marrow fibrosis.
Prevalence of symptoms was assessed with the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.
The retrospective study evaluated if pacritinib increased PLT counts in the phase III PERSIST-2 and phase II PAC203 studies.
Responses in hemoglobin, white blood cell, and platelet were 75%, 82%, and 74%, respectively, at 24 weeks.
Multivariable modeling showed a notable reduction in the risk of GVHD or relapse in the ATG group.
Hemoglobin and platelets are correlated with OS, while mutations in ASXL1, EZH2, IDH1/2, U2AF1, and SRSF2 are not.
Bomedemstat is an oral lysine-specific demethylase-1 (LSD1) inhibitor clinically active in patients with MPNs.
The model could be helpful in understanding fibrotic progression in JAK2V617F mutation–positive MPNs.
The study aimed to address “a substantial unmet need for therapies that alter disease trajectory" in patients with MF.
Ruben Mesa, MD, discussed the results at the 65th ASH Annual Meeting and Exposition.
The use of combination therapies including XPO1 inhibitor selinexor is a potentially effective therapeutic strategy in MF.
This is just one finding from a longitudinal analysis of phase III data from the SIMPLIFY-1 and MOMENTUM trials.
Review more from the post-hoc time-dependent analysis of the phase III Simplify-1, Simplify-2, and MOMENTUM trials.
Led by Dr. Lindsay Rein, the goal of the phase I/II trial was to evaluate the safety and efficacy of TP-3654.
The multicenter trial studied genetic mutations across three cohorts.
Researchers also observed potential disease modification via rapid stabilization of platelets and stable hemoglobin levels.
There were no significant differences in response rates with pegylated interferon-alpha versus hydroxyurea in MPN treatment.
The trial is based on “compelling data” from arm III of the ongoing phase II MANIFEST study.
82.5% of MF patients experienced rapid significant decreases in palpable spleen size after two months of ruxolitinib therapy.
The median duration of therapy is around three years in patients with intermediate or high-risk MF.
The analysis included 346 patients with CALR-mutated MF who were transplanted in 123 centers between 2005 and 2019.
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Section Editor
Douglas Tremblay, MDAssistant Professor of Medicine | Icahn School of Medicine at Mount Sinai
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