Tag Archives: mpn treatment

Evolving Myelofibrosis Treatments Aims to Fill Unmet Needs

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May 21, 2025

Author(s): Ryan Scott

Fact checked by: Spencer Feldman

Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasms (MPN) and can occur as de novo disease. Myelofibrosis creates varying degrees of fibrosis and can cause driver mutations such as JAK2, CALR or MPL in approximately 90% of patients. These mutations cause constant activation of the JAK-STAT pathway, which can lead to uncontrolled cell growth.

Other mutations that can occur, such as ASXL1, SRSF2, EZH2, IDH1/2 and U2AF1, may also affect how the disease develops and prognosis. Moreover, common symptoms of the disease include fatigue, night sweats, fever, bone pain, cachexia, pruritus, thrombosis, and bleeding. Although disease progression is the most common reason for death and occurs in approximately 20% of patients, many patients also face serious risks from other complications. These include heart problems, infections, or bleeding due to low blood counts.

To combat the unmet needs within the myelofibrosis treatment landscape, there have been a number of studies investigating novel treatments for JAK inhibitor-ineligible or relapsed/refractory patients. To further explore these investigations, and the current and future states of the treatment landscapes, investigators broke everything down in research published in the American Journal of Hematology.

Understanding the Present Landscape and Ongoing Studies

The discovery of genetic mutations, as well as the role of the JAK-STAT pathway in the treatment of MPNs has led to the development of oral KAK inhibitors. These drugs work by blocking overactive JAK signaling involved in disease progression and symptom burden.

One such drug being used is Rituxan (ruxolitinib), which is the first ever U.S. Food and Drug Administration (FDA)-approved JAK inhibitor for myelofibrosis, approved by the regulatory agency in 2011. The agent elicits effective for symptom relief and spleen size reduction in approximately 50% of patients who are treated with it.

Common side effects of Rituxan include anemia and low platelets; other non-blood-related side effects include fatigue, diarrhea and infections. Long-term use of the agent may also increase the risk of secondary cancers (like non-melanoma skin cancer) and round 40% to 50% of individuals discontinue the drug within three years due to side effects or lack of efficacy. However, stopping Rituxan is linked to new mutations and poorer outcomes.

Another agent used in the treatment of myelofibrosis is Inrebic (fedratinib), which was approved in 2019 by the FDA for both patients with newly diagnosed disease and those who are refractory and/or intolerant to Rituxan. This agent provides similar benefits to those seen with Rituxan, including reduction of spleen size and symptoms, but with frequent gastrointestinal side effects, like nausea, diarrhea and vomiting.

Notably, Inrebic carries a black box warning for risk of Wernicke’s encephalopathy, making monitoring essential. Additionally, treatment with the agent is less effective in patients who were on high-dose Rituxan prior to switching.

Vonjo (pacritinib) is another treatment which was approved in 2022 for patients with severe low platelet counts in the myelofibrosis treatment space. Unlike Rituxan and Inrebic, it can be used in high-risk patients with more advanced disease and cytopenias. In trials such as the PERSIST-1 and PERSIST-2 studies, Vonjo showed modest spleen and symptom response but improved transfusion independence.

Vonjo is currently being tested in the PACIFICA trial for patients with platelets less than 50 × 10⁹/L.

Finally, Ojjaara (momelotinib) is also being used in the treatment space for patients with this disease and was approved by the FDA in 2023. Ojjaara targets JAK1/2 and ALK2, with a unique effect on anemia. Trials, including the SIMPLIFY-1 and SIMPLIFY-2 studies, showed similar spleen responses to Rituxan but greater improvements in anemia and transfusion independence.

The MOMENTUM study confirmed Ojjaara’s improved both symptoms and anemia in symptomatic, anemic patients previously treated with a JAK inhibitor.

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Interferon Lowers Myelofibrosis Risk in Young Patients With Polycythemia Vera, Essential Thrombocytopenia

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May 15, 2025

Author(s): Alexandra Gerlach, Associate Editor

Early treatment with interferon reduced secondary myelofibrosis (sMF) risk in adolescent and young adult (AYA) patients with polycythemia vera (PV) or essential thrombocytopenia (ET), according to study data published in Leukemia.1

Red blood cells | Image Credit: © fotogurmespb - stock.adobe.com

MF is an incurable, rare hematologic malignancy characterized by the overproduction of red blood cells. This causes bone marrow scarring, which leads to severe anemia—a key factor impacting overall survival (OS) for patients with MF. It can develop as a primary disease or secondary to ET and PV, as well as progress to acute myeloid leukemia in some cases. Although MF is primarily diagnosed in older adults, 20% of cases are in individuals under the age of 40.1,2

AYA patients with ET or PV face unique clinical challenges due to their longer life expectancy because of a lack of data on long-term outcomes and treatment strategies. Existing guidelines are specific to older populations, despite the unique clinical considerations in younger patients.1

“These patients are expected to live for several decades, and the accumulation of additional thrombotic risk factors (age, cardiovascular conditions, additional mutations) may progressively heighten this risk,” the authors wrote. “This highlights a substantial and emerging concern regarding thrombotic events in this younger demographic.”1

The study evaluates complication rates, including thrombosis and progression to sMF, and the impact of interferon (IFN) on outcomes in patients diagnosed before the age of 25. The primary outcomes of the study were thrombosis-free survival (TFS), myelofibrosis-free survival (MFS), and OS in the entire cohort and for ET and PV patients separately, and the impact of treatment on these outcomes. Secondary outcomes were identification of risk factors associated with thrombotic events and sMF.1

The study included a total of 348 patients, of whom 278 were diagnosed with ET and 70 with PV, with a median age at diagnosis of 20 years. The incidence of thrombotic events was about 1.9 per 100 patient-years, with elevated white blood cell count (≥ 11 × 109/L) and absence of splenomegaly at diagnosis identified as significant risk factors. However, cytoreductive therapy did not reduce thrombotic risk. The incidence of sMF was 0.7 per 100 patient-years, with CALR mutations and a history of thrombosis associated with higher risk.1

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FDA Grants Fast Track Designation to Givinostat for Polycythemia Vera

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May 6, 2025

Author(s): Jax DiEugenio

Fact checked by: Chris Ryan

The FDA has granted fast track designation to givinostat (Duvyzat), an orally administered histone deacetylase (HDAC) inhibitor, for the treatment of patients with polycythemia vera (PV).1

The agent is being evaluated in the ongoing phase 3 GIV-IN PV trial (NCT06093672), which aims to compare the efficacy and safety of givinostat to hydroxyurea in patients with JAK2 V617F–positive, high-risk PV, which is characterized by the clonal overproduction of erythroid, myeloid, and megakaryocytic lineages within the bone marrow. By targeting aberrant gene expression, givinostat may suppress pathologic cell proliferation associated with driver mutations such as JAK2 V617F, which are common in patients with PV.

“The FDA decision to grant givinostat fast track designation underscores the urgent need for innovative treatments for PV and highlights the potential of givinostat to make a meaningful difference,” Paolo Bettica, MD, PhD, chief medical officer at Italfarmaco Group, stated in a news release. “We look forward to working closely with the FDA as we plan for completion of our phase 3 clinical trial.”

The FDA and European Medicines Agency both previously granted orphan drug designation to givinostat for PV. In the United States, the FDA previously approved givinostat for the treatment of patients 6 years of age or older with Duchenne muscular dystrophy.2

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Emerging Therapies in Myelofibrosis Could Extend Beyond JAK Inhibitors

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March 24, 2025

Author(s): Ashley Chan

Fact checked by: Ashling Wahner

The September 2023 FDA approval of momelotinib (Ojjaara) for the treatment of patients with primary and secondary myelofibrosis with anemia provided the treatment paradigm with its fourth FDA-approved JAK inhibitor, a class of drugs that has helped improve symptoms associated with myelofibrosis and decrease spleen size, according to Raajit Rampal, MD, PhD.

Additional classes of drugs, such as BET inhibitors and immunotherapy agents, are also currently under investigation in clinical trials and could become “game-changers” if effective, Rampal noted.

“The major [message is] that myelofibrosis is not a monolithic disease, and the selection of the treatment needs to be tailored to the underlying issues and challenges the patient is facing,” said Rampal in an interview with OncLive®.

In the interview, Rampal discussed currently available JAK inhibitors and their limitations, emerging treatments for myelofibrosis, tips for treatment selection, and his takeaways from the 6th Annual Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies.

Rampal is a hematologist-oncologist, the director of the Center for Hematologic Malignancies, and the director of the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center in New York, New York.

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Dr Bhat on the Influence of MPN Risk Stratification on Treatment Decision-Making

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March 20, 2025

Author(s): Seema A. Bhat, MD

Fact checked by: Ashling Wahner, Courtney Flaherty

Seema A. Bhat, MD, a hematologist at The Ohio State University Comprehensive Cancer Center—James; as well as an assistant professor in the Department of Internal Medicine in the Division of Hematology at The Ohio State University, discusses the importance of risk stratification for navigating treatment selection for patients with myeloproliferative neoplasms (MPNs).

Stratifying patients with MPNs into appropriate risk groups is crucial for treatment decision-making, as patients’ individual risk factors strongly factor into selection, Bhat says. Typically, patients with low-risk disease will receive treatments directed at symptom management, whereas cytoreductive agents like hydroxyurea, as well as targeted therapies like JAK inhibitors, are considered for patients with high-risk disease, she explains. Furthermore, allogeneic stem cell transplantation may be a curative treatment option for patients with very high–risk MPNs, she notes.

The revised IPSET Thrombosis Score is used for essential thrombocythemia (ET) risk stratification. Patients are considered to have low-risk polycythemia vera (PV) if they are younger than 60 years of age and have no history of thrombosis; patients are considered to have high-risk PV if they are older than 60 years of age and/or have a thrombosis history.

Four JAK inhibitors are FDA approved for the treatment of patients with MPNs. Ruxolitinib (Jakafi) is indicated for adult patients with intermediate- or high-risk myelofibrosis, including primary myelofibrosis and secondary (post-PV or post-ET) myelofibrosis; as well as adult patients with PV who have had an inadequate response or are intolerant to hydroxyurea. Fedratinib (Inrebic) is approved for adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. Pacritinib (Vonjo) is indicated for use in adult patients with intermediate- or high-risk primary or secondary myelofibrosis with a platelet count below 50 × 109 /L. Finally, momelotinib (Ojjaara) is approved for adult patients with intermediate- or high-risk primary or secondary myelofibrosis with anemia.

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Options for MPN Treatment Are Expanding Rapidly With More on the Horizon

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December 24, 2024

Author(s): Laura Joszt, MA, Luke Halpern

The past few years have been an exciting time in myeloproliferative neoplasms (MPNs) with new treatments providing new options for patients and additional products in the pipeline that explore new mechanisms of action, explained Firas El Chaer, MD, associate professor of medicine, University of Virginia School of Medicine. At the American Society of Hematology annual meeting, El Chaer had presented research and been a coauthor on abstracts related to treatment for myeloproliferative neoplasms.

He discussed how MPNs are diagnosed, the current treatment landscape, and promising new therapies in the pipeline. When diagnosing for MPNs, particularly for myelofibrosis, a bone marrow biopsy is needed, but the challenge is that this can be “patchy,” he explained, and the amount of fibrosis present in the particular part of the bone marrow that is biopsied is what is relied upon to make the diagnosis.

The good news is that the approval of many new Janus kinase inhibitors has changed the treatment landscape of myelofibrosis dramatically in the last few years, El Chaer said, which has provided patients with additional options for treatment. In addition, there are new mechanisms of action that can improve anemia in this patient population.

“I’m very excited that currently we’re thinking about combination therapies,” he said, to improve anemia or that potentially have a disease-modifying capability. “Our field is expanding very quickly.”

He highlighted some of the new mechanisms of action being studied in myeloproliferative neoplasms, such as bromodomain molecules and TGF-β agonists, which can potentially be helpful for anemia and this patient population. He had presented phase 1/2 data on nuvisertib, or TP-3654, which is a highly selective PIM1 kinase inhibitor that has reduced spleen size and bone marrow fibrosis either alone or in combination with ruxolitinib. Nuvisertib has minimal cytopenia side effect and can be combined with other molecules for treatment. Currently, enrollment is ongoing in 3 arms of the study (NCT04176198) to continue to evaluate nuvisertib as a monotherapy and in combination with ruxolitinib and momelotinib.

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Emerging Data Continue to Evolve Treatment Utilization in MPNs

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Laura Joszt, MA

Emerging data are continually changing the knowledge base around how interferons should be used, despite being around for decades, in patients with myeloproliferative neoplasms (MPNs), says Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

Transcript

How has the landscape for MPN treatment evolved since the introduction of interferons? How does it look different today?

I guess it’s more a question of utilization than the landscape, in the sense that both things like hydroxyurea and interferons and drugs, like an anagrelide for ET [essential thrombocythemia], have been around for quite some time. And I think that it hasn’t been clear for the majority of that time which drugs should be used when and by whom.

There is now randomized clinical trial data for pegylated interferon vs hydroxyurea, but more recently, particularly with regards to polycythemia vera, there’s randomized data with ropeginterferon and hydroxyurea. And at least in that data set, the [blood] count control was superior with ropeginterferon vs hydroxyurea over the course of a number of years. Initially, at 1 year, there wasn’t so much of a difference, but as time went on, there was clearly a difference that favored the use of ropeginterferon in terms of controlling the blood counts. Similarly, over time, there does seem to be a decrease in the JAK [Janus kinase] 2 mutation burden in the patients who got the ropeginterferon.

I think that there is an emerging data set that is arguing that there are benefits to interferon. Going back to the initial point here, the landscape has changed to some degree—with the introduction of something like ropeginterferon—but I think it’s more that the data is evolving, which is beginning to tell us maybe which drugs might be best for which patients. We’re not completely there by any stretch of the imagination, but the data is beginning to coalesce around the message.

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A Parent’s Story: Navigating the Health Insurance Maze

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By Sarah W.

Sarah is a member of MPN Advocacy & Education International’s Patient Advisory Council

I know there are good people who work at insurance companies, however, some are the bane of my existence. Every month I gear up for the fight to get my son, Jedi, his medicine. Jedi has an MPN. My hope is that my journey can be used to make this process easier and better for other patients and their families.

Hydroxyurea was the initial drug prescribed for my son. It wasn’t a difficult drug to get filled, even though it was a little overwhelming walking my son through the adult oncology unit at MD Anderson Cancer Center, to the “specialty pharmacy.” It was frightening for him to see adults that look so sickly skinny and with their bald heads from their treatments. However, the real frustration began when he was put on Pegasys. MD Anderson tried to call numerous pharmacies to his prescription filled, but they were unable to find a pharmacy that had it in stock. So we left the hospital with a handwritten script in search of the drug.

Read tips from Speciality Pharmacist/MPN Patient Jennifer Powers w/ links to treatment assistance programs

At that time, we were insured by United Health Care. This was my first introduction to a specialty drug. For background purposes, specialty drugs are a recent designation of pharmaceuticals that are classified as high-cost, high complexity and/or high touch, such as injectables. A chemotherapy that is administered orally, like Hydroxyurea, is covered as part of a normal prescription. A chemotherapy that is administered as a subcutaneous (jiggly fat) shot, like Pegasys, is not. In other words, it comes out of your deductible. For us, that means we owed approximately $4,000 for the first month of Pegasys. We had to prove to the insurance company that Pegasys had been approved for polycythemia vera. This was done by producing a memo my husband found on the internet from United Health Care specifically stating Pegasys was approved for polycythemia vera.

Then, our insurance was switched to Blue Cross Blue Shield of Texas (BCBSTX). (I will skip the conversation about trying to get our member number early so I could start the pre-approval process.  I had been told in a Facebook group that it took about six weeks to approve Pegasys with BCBS. This was cause for concern because we could only get four weeks of medicine at a time.)

I started the pre-approval process with BCBS after we received a member ID number the first week of January. As expected, Pegasys was initially declined.  In the state of Texas I should be able to submit an emergency appeal and get a response in three days, but I had to get the appeal submitted first.  It is very difficult to get the appeal started. Not to mention that BCBSTX outsources the pharmaceuticals to Prime.

After a few weeks of deep frustration and the looming possibility we could run out of his medication, I finally posted the following on Blue Cross Blue Shield of Texas Facebook page:

January 15, 2019. Your appeals process is TERRIBLE. I have spent HOURS trying to figure this out. I have a 10 year old with CANCER. His medicine is out next week. I have to get it from a specialty pharmacy. His doctor called BCBS yesterday (a number I got after spending TWO HOURS on the phone last Friday) and was told that he has to wait 7-10 business days to start the process. Today I received a NEW peer-to-peer phone number. Does this start the process? No, it sets up an appointment for our doctor to talk to your doctors. Just to give you an idea. This medicine controls platelets. If his platelets go up he could have a heart attack, stroke, embolism for example. You can see my concern. My next steps are to ask my doctor to call AGAIN to START the appeals process – you know the one he tried to start yesterday? I will also have on my TO DO list to file a complaint with Texas Department of Insurance, contact my state Senator and Representative. Thank you for making this such a HARD process. Oh, by the way, the National Comprehensive Cancer Network, other BCBS insurance (different states), United Healthcare ALL have approved this medicine for his diagnosis

 I received a phone call from BCBSTX within 24 hours of posting this. I was told I had made it to the “special escalation” team because I posted on social media. On one hand, I am grateful he was approved. On the other hand, I am sad that this is what it took. I think it also helped that I had gathered the information to make it easy for them to approve. I had whitepapers, Jedi’s medical records and the details from the National Comprehensive Cancer Network. (Click here to view).

I wish I could say this was the end of the drama. But this is a story for another day. Just writing this was overwhelming. I can’t imagine what people who are sick go through. I am the caregiver, not the patient. I do not have chemo brain and I am exhausted by the process and the stress and anxiety to ensure my child receives his treatment. I hope this information will help other families move through the process a little more smoothly and I will continue to write about the trial and tribulations I experience on my website.

View Videos from the MPN Pediatric & Young Adult Program in 2018