Tag Archives: myelofibrosis

Clinical Trial Aims to Test Tagraxofusp and Pacritinib Combination Therapy in Patients With MF

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Özge Özkaya, MSc, PhD
Publish Date

A new study testing the combination of tagraxofusp and pacritinib in patients with myelofibrosis (MF) is now open.

The single-center, open-label, early phase 1, pilot trial aims to recruit 20 patients with MF who are at least 18 years of age and who have previously been treated with a Janus kinase (JAK) 1/2 inhibitor or in whom JAK1/2 inhibitor therapy is not appropriate, is contraindicated, or was declined.

Participants will be given 12 µg/kg of intravenous tagraxofusp once a day for 3 consecutive days and 200 mg of oral pacritinib twice a day starting at the 4th day of the second cycle and administered continuously with subsequent cycles starting on day 1 of each cycle.

The primary outcome measures will be a spleen volume reduction of 35% of more and the change in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score Version 2.0 (MPN-SAF TSS 2.0) from baseline to week 24.

Secondary outcome measures will include the number of participants with treatment-related adverse events, the change from baseline in anemia and platelet count, and any improvement in patients’ quality of life based on the global impression of change.

Tagraxofusp is a cytotoxin directed at CD123, and pacritinib is a small-molecule kinase inhibitor. The rationale of using these 2 drugs in combination is their compatible mechanisms of action targeting MF stem cells and the bone marrow. It is thought that the combination may lead to improvements in symptoms associated with myeloproliferative neoplasms and reduce splenomegaly.

Both agents have previously been studied in cases of mildly depleted bone marrow and were shown to be safe and led to hematological improvements.

The trial is not yet recruiting participants but aims to recruit 20 participants. It is estimated to be completed in December 2026.

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Real-World Findings Confirm Clinical Data on Momelotinib in MF With Anemia

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May 1, 2025

Author(s): AJMC Contributor

Real-world insights on momelotinib (Ojjaara; GlaxoSmithKline) in patients with myelofibrosis (MF) and anemia have been published, showing consistent and, in some cases, better results than those shown previously in clinical studies of the drug.1

The results offer some of the first glimpses into real-world findings of the Janus kinase (JAK) inhibitor, which received approval toward the end of 2023, becoming the first and only treatment indicated for patients with MF and anemia.2

“This study presents the largest real-world cohort of MF patients treated with momelotinib and is the first to apply the recently proposed 2024 criteria for anemia response,” wrote the researchers, publishing the insights in Blood Cancer Journal.1

The retrospective study included 122 patients with MF and anemia across multiple treatment centers. Patients had disease-related symptoms or symptomatic splenomegaly and could be JAK-naive (23.4%) or previously received treatment with a JAK inhibitor (76.6%).

At treatment initiation, 73.8% of patients were dependent on transfusions. Among these patients, the median Hb level increased from 7.7 g/dL (range, 4.7-9.8) at treatment initiation to 8.7 g/dL at 3 months of follow-up. By 6 months, 30.6% of patients had major responses and 36.1% had minor responses. At the time follow-up point, median red blood cell transfusion frequency had dropped from 4 units per month to 1 unit per month.

The results offer some of the first glimpses into real-world findings of the JAK inhibitor momelotinib, which was approved in 2023.

Among the remaining patients who were not dependent on transfusions at treatment initiation, the median Hb level increased from 8.9 g/dL (range, 7.2-10.8) to 10.2 g/dL. At 6 months of follow-up, 36.4% of patients demonstrated a major response, and 27.3% demonstrated a minor response.

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Biomed Valley Discoveries Announces First Patient Dosed in Phase 1/2 Combination Study of Ulixertinib with Ruxolitinib (Jakafi®) in Patients with Myelofibrosis

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Provided by GlobeNewswire  

— Dual targeting of JAK 1/2 (ruxolitinib) and ERK 1/2 (ulixertinib) may represent a novel treatment approach for myelofibrosis and possibly other myeloproliferative neoplasms

KANSAS CITY, Mo., April 28, 2025 (GLOBE NEWSWIRE) — Biomed Valley Discoveries (BVD), a clinical-stage biotechnology company guided by its founders’ intent of bringing hope for life to patients, today announced that the first patient has been dosed in a Phase 1/2 combination study of ulixertinib, BVD’s highly selective, first-in-class ERK 1/2 inhibitor with ruxolitinib, a JAK1/JAK2 inhibitor for the treatment of myelofibrosis, a rare type of bone marrow cancer that disrupts the body’s normal production of blood cells.

Raajit Rampal, M.D., Ph.D., a hematologist-oncologist with Memorial Sloan Kettering Cancer Center who specializes in the treatment of myeloproliferative neoplasms and leukemia, is the lead principal investigator for this investigator-initiated trial.

“We’re thrilled to announce the milestone of first patient dosed in this trial, and grateful for the opportunity to collaborate with Dr. Rampal and Incyte to explore the potential of ERK inhibition as a complement to JAK inhibition for the treatment of patients with myelofibrosis,” said Brent Kreider, Ph.D., President of BVD. “This trial helps further our commitment to fully interrogate the potential of direct ERK inhibition to address unmet patient needs in various cancer settings where MAPK signaling is implicated.”

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Disc Medicine to Host Webinar with Key Opinion Leaders on Anemia of Myelofibrosis (MF)

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Disc Medicine Inc – (GLOBE NEWSWIRE)

April 29, 2025

WATERTOWN, Mass., April 29, 2025 (GLOBE NEWSWIRE) — Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, today announced it will host a virtual KOL investor event on Friday, May 9 at 1:00 PM ET / 10:00 AM PT to provide an overview of anemia of myelofibrosis (MF) and discuss the evolving treatment landscape for this disease. The event will also include an overview of Disc’s clinical data and development plans for DISC-0974 in MF anemia.

Intended for investors and other interested audiences, the virtual event will feature presentations from leading experts on myeloproliferative neoplasms (MPNs), including MF. The KOL speakers will provide an overview of MF anemia, its epidemiology, pathogenesis, and impact on patients, then discuss the current and emerging therapeutic landscape for MF and highlight the clear unmet need for anemia-focused treatments. Invited speakers include:

  • Dr. Aaron Gerds, M.D., M.S., a hematologist-oncologist at Cleveland Clinic and associate professor at Case Western University School of Medicine, where he runs the cancer center’s Clinical Research Office. Dr. Gerds has been a principal investigator in various clinical trials for MPNs.
  • Dr. Prithviraj Bose, M.D., a professor at MD Anderson Cancer Center with a focus on MPNs. Dr. Bose has been a leader in multiple clinical trials in myelofibrosis.

Members of Disc’s leadership team will review the therapeutic rationale for DISC-0974, summarize clinical data from the Phase 1b trial of DISC-0974 in MF anemia originally presented at the 2024 American Society of Hematology (ASH) annual meeting, discuss the design for its ongoing Phase 2 trial, and reiterate expected timing for an interim Phase 2 data readout in 2025. Management will also provide a view of the expected market opportunity and positioning for DISC-0974 in MF anemia.

A live webcast of the event will be available in the Events and Presentations section of the Investor Relations page of Disc’s website (https://ir.discmedicine.com/). A webcast replay will be available after the live presentation and will be accessible for 90 days. Please register for the event on the Events and Presentations page of Disc’s website ( https://edge.media-server.com/mmc/p/5c72d8fu ).

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Molecular predictors of venous and arterial thrombotic events in patients with myelofibrosis

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Olga Morath, Jenny Rinke, Annabell Walter, Carl Crodel, Manja Meggendorfer, Constance Baer, Andreas Hochhaus & Thomas Ernst

Abstract

While patients with myelofibrosis (MF) face an elevated risk of thrombosis, no validated scoring system currently exists to effectively assess this specific risk. This study aimed to explore distinct molecular risk factors for arterial (ATE) and venous (VTE) thrombosis in a cohort of 141 MF patients. Mutation analysis was performed by next-generation sequencing for a panel of 30 target myeloid genes as previously described: 137 driver and 164 non-driver mutations were detected. JAK2-V617F was identified in 77 (55%) patients, CALR in 45 (32%) patients, and seven (5%) patients carried an MPL variant. Patients #58 and #60 harbored JAK2-V617F and MPL; and patient #67 was positive for all three driver genes. The JAK2–V617F variant allele frequency (VAF) was assessed in 66/80 patients, revealing a median of 34.0% (range, 5.0–96.0). ASXL1 (n = 34 patients) were the most common non-driver mutations, followed by TET2 (n = 26), U2AF1 (n = 12), and DNMT3A (n = 11). During a median follow up of 4.8 years, 24 (17%) patients experienced VTE, 15 (11%) ATE, and two patients experienced both. Among the 24 patients with VTE, 12 (50%) experienced splanchnic vein thrombosis. The JAK2-V617F mutation was associated with VTE (OR 2.6, 95% CI 1.01–7.16), while the DNMT3A mutation was an independent predictor of ATE (OR 5.40, 95% CI 1.30-22.42). High JAK2-V617F VAF (> 50%) was not related with an increased thrombotic risk. Results of this study demonstrate the significance of DNMT3A mutations as an independent molecular risk factor for ATE, highlighting the potential to include these somatic non-driver mutations in future thrombosis risk scores.

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As-Expected Ruxolitinib Starting Dose Outperforms Lower Dosage in Myelofibrosis

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By Bridget Hoyt
Fact checked by Kristie L. Kahl

Patients with myelofibrosis who were treated with the expected starting dose of ruxolitinib (Jakafi) demonstrated higher spleen response rates and a shorter median time to first response vs patients receiving a less-than-expected starting dose, per data from the ROMEI trial.

Additionally, overall survival (OS) was not reached in the as-expected group; however, patients in both groups reduced daily dosages over 12 months in the multicenter, observational, ongoing study, according to findings published in Cancer.

“To ensure optimal treatment with ruxolitinib, patients should be started on appropriate ruxolitinib doses and maintain the highest tolerated dose for maximum effectiveness,” wrote the study authors. “Patients who received the recommended doses showed a better trend in response.”

Trial Design and Key Data

The trial enrolled 508 adult ruxolitinib-naive patients who had been diagnosed with primary or secondary myelofibrosis across 51 centers in Italy between April 2017 and May 2022, at which time ruxolitinib was the only FDA-approved JAK inhibitor for myelofibrosis.

Patients with available baseline platelet counts were stratified into the as-expected (n = 174) and lower-than-expected (n = 132) dosage groups, resulting in 43% of patients receiving a lower-than-expected dose.

Changes in symptoms and health-related quality of life (HRQOL), assessed using Myeloproliferative Neoplasm 10 total symptom score (MPN-10 TSS) and EuroQol5-Dimension 5-Level (EQ-5D-5L), respectively, were primary end points of the study.

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Assessing Risk for JAK Inhibitor Selection in Myelofibrosis

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By Targeted Oncology Staff

In part 1, experts explores how assessing individual risk factors is crucial in selecting the appropriate JAK inhibitor for patients with myelofibrosis.

CASE

AARON T. GERDS, MD, MS: How do you use molecular testing, bone marrow results, and clinical features to stratify risk in patients with myelofibrosis?

PRITHVIRAJ BOSE, MD: At this point, I believe we are all receiving the myeloid mutation panels. We also order JAK2, MPL, and CALR: the 3 drivers. However, most clinicians would order a myeloid mutation panel because we know that many of the mutations are prognostic. This is the whole point of risk stratification, which is now increasingly sophisticated and integrates multiple clinical, molecular, [and] cytogenetic variables to determine who needs a transplant.

These are the first actions I take when speaking with a new patient. I get an idea of their risk in terms of survival and prognosis, and that informs my decision to refer them to transplant. I then counsel the patient appropriately.

I do not believe molecular testing informs treatment because our drugs are, for the most part, mutation agnostic. All we have are JAK inhibitors, which are not mutation specific. However, from a prognostic standpoint, the [role] of molecular testing is key.

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Protein Disulfide Isomerase Could Be Therapeutic Target for MF

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Özge Özkaya, MSc, PhD
Publish Date

Protein disulfide isomerase may be involved in the underlying pathogenesis of thrombotic events in Philadelphia-negative myeloproliferative neoplasms such as myelofibrosis (MF), according to a new study published in the Egyptian Journal of Internal Medicine.

It could also be valuable in predicting the risk of developing thromboembolic events, the researchers noted.

These findings suggest that protein disulfide isomerase could be used as a therapeutic target to prevent thrombotic events in patients with MF and other myeloproliferative neoplasms.

For the study, a team of researchers, led by Mai Galal Elshenoufy, MD, PhD, from Cairo University in Egypt, measured the levels of protein disulfide isomerase in the serum of patients with myeloproliferative neoplasms and assessed its role as a possible marker of increased risk of thromboembolic events.

They found that the levels of the enzyme were pathologically high in the serum of patients with myeloproliferative neoplasms compared to controls. The levels were also higher in patients with arterial thrombosis, but this finding had no statistical significance.

Future work should evaluate the levels of protein disulfide isomerase in a larger group of patients with myeloproliferative neoplasm with and without thrombotic events, and in patients with arterial versus venous thrombosis, they said.

Finally, measuring the levels of protein disulfide isomerase before and after aspirin therapy could give clues about the effect of this treatment, they added.

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Dr Harrison on Factors Influencing Patient Prognosis and Treatment Selection in Myelofibrosis

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April, 22, 2025

Author(s): Claire Harrison, MD, FRCP, FRCPath

Fact checked by: Ashling Wahner ,Courtney Flaherty

Claire Harrison, MD, FRCP, FRCPath, a professor of myeloproliferative neoplasms, a consultant, and a clinical director at Guy’s and St. Thomas’ Hospital, discussed the general treatment algorithm for myelofibrosis management, as well as how certain mutations affect patient prognosis and treatment decision-making.

Myelofibrosis is a heterogeneous myeloproliferative neoplasm with significant variability in clinical presentation and disease trajectory, Harrison began. Accurate diagnosis is the foundational step, necessitating careful review of histopathology, peripheral blood findings, bone marrow morphology, and molecular genetics—even in patients who have been referred from other institutions, she stated. Key diagnostic indicators include the presence of splenomegaly and constitutional symptoms, as well as driver mutations, such as JAK2, CALR, and MPL, which support a diagnosis of myeloproliferative neoplasm, Harrison detailed.

Furthermore, assessment of patient-specific factors is essential to inform therapeutic strategy, she continued. This includes evaluating comorbid conditions that may limit treatment options and determining the dominant clinical manifestations of each patient’s disease, Harrison noted. Patient education plays a critical role in this step, with efforts made by oncologists to ensure patient comprehension of the diagnosis—often explicitly referring to myelofibrosis as a “blood cancer”—and to connect patients with advocacy resources when appropriate, she explained.

Prognostication in myelofibrosis incorporates multiple validated models, with modern tools integrating both clinical and molecular data, Harrison said. Driver mutations aid diagnostic classification; however, the absence of these mutations in triple-negative cases warrants expanded next-generation sequencing to identify alternative pathogenic mutations, according to Harrison. The presence of high molecular risk mutations—including ASXL1, IDH1/2, SRSF2, U2AF1, TP53, RUNX1, and NRAS—portends a poorer prognosis and should influence risk stratification and treatment planning, Harrison concluded.

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Real world outcomes of momelotinib in myelofibrosis patients with anemia: results from the MOMGEMFIN study

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Lucía Pérez-Lamas, Adrián Segura Diaz, Regina García Delgado, Alberto Álvarez-Larrán, María Alicia Senin, Elvira Mora, María Laura Fox, Irene Pastor Galan, Gemma Azaceta, et al.

Standard treatment for symptomatic myelofibrosis (MF) patients includes JAK inhibitors (JAKi) like ruxolitinib and fedratinib [1,2,3,4], but their effectiveness is often limited by transient responses and the development of cytopenias [5]. Recently, momelotinib received FDA and EMA approval for treating splenomegaly and disease-related symptoms in adult patients with MF and anemia. In addition to JAK1/JAK2 inhibition, momelotinib targets the activin A receptor type 1 (ACVR1), which regulates iron metabolism through hepcidin, contributing to its unique therapeutic profile [6]. The efficacy of momelotinib in improving symptoms, reducing spleen size, increasing hemoglobin (Hb) levels, and reducing transfusion dependency in both JAKi naïve and JAKi exposed MF patients has been demonstrated in several clinical trials [7,8,9,10,11].

Given its recent approval, real-world data on momelotinib use is still limited. To gather evidence on its efficacy and safety in routine practice, the Spanish Group of Philadelphia-negative Myeloproliferative Neoplasms (GEMFIN) initiated the MOMGEMFIN study, analyzing MF patients treated with momelotinib through a managed access program.

This study was a multicenter, retrospective analysis of adult patients treated with momelotinib (JAK-naïve or JAK-exposed) from March 2023 to July 2024. Eligible participants had primary or secondary MF with anemia and disease-related symptoms or symptomatic splenomegaly. Anemia was defined as Hb values less than 11 g/dL for men and less than 10 g/dL for women. Anemia response was based on the 2024 IWG-ELN criteria [12]. Transfusion dependency was classified as requiring at least one red blood cell (RBC) unit per month or three or more units over 12 weeks. Spleen evaluation followed the 2013 ELN (IWG-MRT) criteria [13]. Adverse events (AEs) were graded per CTCAE version 5.0.

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