VENLO, Netherlands & WILMINGTON, Del.–(BUSINESS WIRE)–Jun. 15, 2025– QIAGEN N.V. (NYSE: QGEN; Frankfurt Prime Standard: QIA) and Incyte (Nasdaq: INCY) today announced a new global collaboration to develop a novel diagnostic panel to support Incyte’s extensive portfolio of investigational therapies for patients with myeloproliferative neoplasms (MPNs), a group of rare blood cancers, including Incyte’s monoclonal antibody INCA033989, targeting mutant calreticulin (mutCALR), which is being developed in myelofibrosis (MF) and essential thrombocythemia (ET).
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Positive Late-Breaking Data for Incyte’s First-in-Class mutCALR-targeted therapy INCA033989 in Essential Thrombocythemia Presented at EHA2025
WILMINGTON, Del.–(BUSINESS WIRE)–Jun. 15, 2025– Incyte (Nasdaq:INCY) today announced the first clinical data from two studies evaluating the safety, tolerability and efficacy of INCA033989, a novel, first in class, Incyte-discovered, targeted monoclonal antibody in patients with mutant calreticulin (mutCALR)-expressing myeloproliferative neoplasms (MPNs). These data – featured today in the Late-Breaking Oral Session (#LB4002) at the European Hematology Association 2025 (EHA2025) Congress in Milan, Italy – focus on the dose escalation portion of the studies in patients with high risk essential thrombocythemia (ET) who are resistant/intolerant to prior cytoreductive therapy.
The studies evaluated the safety and efficacy of INCA033989 in patients with ET as measured by hematologic response and reduction in mutCALR variant allele frequency (VAF).
A Commitment to New Therapies for MPN Despite Scientific Challenges
January 2, 2025
Author(s): Darlene Dobkowski, MA
Fact checked by: Alex Biese
A researcher discussed the evolving understanding of myeloproliferative neoplasms (MPNs), from their initial classification to their potential for progression, and emphasized the scientific community’s commitment to developing new therapies despite the inherent challenges of research.
John Crispino, director of the division of experimental hematology at St. Jude Children’s Research Hospital in Memphis, Tennessee, was recognized at the CURE MPN Heroes event for his dedication to the community both through his scientific breakthroughs and his advisory role for the MPN Research Foundation.
CURE also spoke with Crispino about what he has learned about patients with MPNs and the research around the condition over his years in the field. One of the things he mentioned was the disease’s transition from a myeloproliferative disorder to a myeloproliferative neoplasm. In particular, the World Health Organization (WHO) changed the classification of these conditions to MPNs to reflect the understanding that these conditions are a type of cancer.
Q&A: Transforming MPN Care by Aligning Research With Patient-Centered Outcomes
December 26, 2024
Physician’s Weekly (PW) met with John O. Mascarenhas, MD, and Kapila Viges to learn how the latest research impacts care for patients with myeloproliferative neoplasms (MPN).
PW: What do you see as the most beneficial of all the combinations that are being explored right now?
Ms. Viges: It’s important to remember that options matter for patients. In myelofibrosis and MPN, more broadly, these chronic diseases, patients live for decades in relatively stable health. But knowing that there are options over time if something either stops working or their disease progresses, knowing that they can sequence through a few more options and maybe even some newer combinations that are interesting, brings a lot of hope and promise for patients and gives them some comfort as they navigate their journey through their disease.
Dr. Mascarenhas: The key to treating myelofibrosis is that you need options to tailor the therapy. It’s not one treatment fits all. So, whether it’s a monotherapy, a combination, or when to switch, each agent to pick is individualized for the patient. The more options we have as physicians, the more likely we can tailor and optimize a treatment for an individual.
Ms. Viges: That’s our motto—options matter. We at MPN Research Foundation recently surveyed 676 patients to learn their treatment goals. Of these, 50% said improved quality of life. More specifically, 40% said relief from symptoms is their primary goal. Patients value the options coming online, the combinations, and how we measure and manage symptoms.
Dr. Mascarenhas: Symptoms are complex and sometimes hard to measure. It’s hard to measure the actual or absolute benefit of a given therapy or combinations with symptoms. So, it’s been an area in our field for drug development where we’re trying to figure out the best way to capture that benefit for any individual patient because some patients may benefit to greater degrees than others, and not all therapies are ideal for any given patient. It is a complex world that we’re living in in terms of trying to navigate this. But, patients are symptomatic, and they want to feel better. Physicians want to make patients feel better, but we also want to extend survival with good symptomatology. So it’s a mixed picture. For some patients, the symptoms may be systemic or cytokine symptoms.
Do you think trials will continue considering additional endpoints or exploring more markers?
Dr. Mascarenhas: One of the fundamental deficiencies in our field is that we currently measure spleen and symptom reduction as our primary endpoints for clinical trials because we started the field with JAK inhibitors. They don’t do it for everyone perfectly and don’t always maintain it indefinitely for every patient. So that’s some of the nuances, but we are moving into an area where we’re looking now at therapeutics that might be able to change the natural disease history. The problem with the trials we design often is that we don’t follow patients because you need a lot of patients; you need a lot of power to do it.
Statistically, we don’t always follow them to the point where we can confirm survival. So we are in a desperate search for surrogate markers that you can look at earlier on, whether it’s spleen reduction or symptom burden even, or bone marrow fibrosis reduction, driver mutation reduction, cytokine reductions, things that you can measure maybe at a six month period that may correlate and associate down the line with a survival benefit. It’s key for us as investigators and the research foundation to figure out how we do that as a group so that we’re not at the stumbling block where we’re trying to understand what we are achieving.
Role of Long Noncoding RNA Defined in Pathogenesis of MPNs
August 22, 2024
Vicki Moore, PhD
A role for lnc-AC004893, a long noncoding RNA (lncRNA), in the pathogenesis of myeloproliferative neoplasms (MPNs) was revealed in a study reported in the journal Hematology.
“Treatment with JAK2 inhibitors combined with the inhibition of lnc-AC004893 might improve the clinical treatment efficiency in MPN patients,” the study investigators wrote in their report.
A lncRNA is a nonprotein coding transcript with a length of more than 200 nucleotides, which may potentially have a biological function and could be dysregulated in the setting of disease. The investigators set out to explore whether lncRNA may have a role in MPN pathogenesis.
To evaluate this, the investigators conducted lncRNA sequencing from bone marrow mononuclear cells in 3 patients with MPN and 3 control individuals. They identified approximately 500 different lncRNAs that appeared expressed at a level of greater than or less than 2.0-fold in patients with MPN, in comparison with the expression level in control individuals.
From among these lncRNAs, the investigators performed further analyses related to expression and other characteristics. These analyses identified lnc-AC004893 as being of potential interest.
The investigators further evaluated lnc-AC004893 in samples from 150 patients with MPN, compared with 20 control individuals, and identified an approximately 5-fold increase in lncRNA transcript in patients with MPN, compared with the control population.
MPN Word of the Month: Cytokines
MPN Word of the Month:
Cytokines
Recently, I heard someone describe cytokines as ingredients that make up a recipe. The recipe is a response to a specific event. Like, when we make chicken soup when someone we love has a cold. Each person with an MPN has their own special ingredients that come together in response to different events that happen inside and outside of the body.
So what are cytokines, really? Cytokines are tiny proteins secreted by cells to communicate with one another. What do they say? Basically, they say to activate (go from doing nothing to doing something), proliferate (make more cells), or differentiate (become more specialized, like becoming an eye cell or a liver cell).
Cytokines can send messages to increase inflammation (pro-inflammatory), or stop inflammation (anti-inflammatory). Inflammatory cytokines play a role in the development and progression of myeloproliferative neoplasms.
Some research suggests that there are certain cytokines commonly associated with MPNs. For example, IL-1β (Interleukin-1beta), TNF-α (Tumor Necrosis Factor-alpha) , IL-6 (Interleukin-6), IL-8 (Interleukin-8), VEGF (Vascular Endothelial Growth Factor), PDGF (Platelet Derived Growth Factor), TGF-β (Transforming Growth Factor-beta), and IFNs (Interferons). These cytokines are expressed in different ways that may contribute to the various MPN subtypes.
For example, a recipe may call for tomatoes, but there are different kinds of tomatoes based on their individual genetic makeup…Roma tomatoes, San Marzano tomatoes, Cherry tomatoes. This recipe (cytokine expression) can be seen in different subtypes. For example, people with polycythemia vera (PV) have been known to have elevated levels of IL-12, IL-4 and GM-CSF when compared to people with essential thrombocythemia (ET). Some cytokines, such as BLC, Eotaxin-2, M-CSF, and TIMP-1, may one day help diagnose and predict the progression of fibrosis in MPN subtypes.
While it is not completely clear how your cytokine “recipe” can be affected by lifestyle, conventional wisdom tells us that healthy lifestyle changes can’t hurt. Reducing additional inflammation that may occur through lifestyle choices could help to support your body in ways that impact your experience of your symptoms at the least. A healthy diet, exercise, and stress reduction have all been associated with lowering inflammation in the body.
Individualized Approaches and Challenges in Myelofibrosis
Raajit Rampal, MD, PhD
Raajit K. Rampal, MD, PhD, hematologic oncologist at Memorial Sloan Kettering Cancer Center, discusses how the field of gene therapy and precision medicine is evolving in the context of myelofibrosis treatment. He also explains how treatment decisions are individualized for patients with myeloproliferative neoplasms, including myelofibrosis.
Rampal presented on this topic and more at the Fifth Annual Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies, hosted by Dr. Guenther Koehne and Miami Cancer Institute.
In addition, Rampal discusses some of the unmet needs that exist in this space, including the need for disease-modifying therapy in this interview with Targeted OncologyTM.
A Grand Time in Grand Rapids
MPN Advocacy & Education International held an in-person patient/caregiver event in Grand Rapids, Michigan on April 25th. The room buzzed with excitement and camaraderie as patients and caregivers had the opportunity to engage with each other and MPN experts on a wide range of topics.
Dr. Anas Al-Janadi gave an overview of the history of MPNs and defined where we are in our current understanding of the disease and what the future may hold. While exciting discoveries were made that supported the development of drug therapies for MPN patients; such as the JAK2 mutation in 2005 and later the MPL and CALR mutations, the MPN community is still working to better understand the reasons for disease progression and ways to reduce symptom burden.
Dr. Kristin Pettit, on the heels of her wedding (Congrats, Dr. Pettit), discussed the challenges MPN patients have flying, having elective or emergency surgeries, symptom management, and some critical women’s issues. Each topic had the following take-aways: check with your doctor and practice good self-care. Dr. Pettit emphasized hydration, healthy eating, exercise and reducing stress.
Dr. Aaron Gerds shared a play-by-play of diagnosing and treating MPNs. He began by situating ET, PV, and MF on the greater spectrum of Myeloid Neoplasms. Dr. Gerds, along with the other experts that presented, stressed the importance of a good clinical examination including a thorough history and a hands-on physical examination. Gerds went on to describe the testing required to make a proper MPN diagnosis, such as; blood counts, chemistries, infectious disease, bone marrow biopsy, and molecular testing. Afterwards, he walked us through the process of navigating individual risk and treatment options using the National Comprehensive Cancer Network (NCCN) Guidelines for Myelofibrosis.
Justin Grinell, owner and head trainer of State of Fitness, reminded us that our health is not our fault, but it is our responsibility. He shared some ways to move toward a healthy lifestyle by incorporating an 11 min movement break in our day. To take just 11 minutes each day doing something active at your own Zone 2 (when your heart rate is 180 minus your age) can have an accumulative positive effect on not just your body but on your brain as well. Be sure to look for Justin this summer during our Healthy Summer Series webinars where you can join Justin for a quick lunch-time workout.
Finally, Dr. Craig Kessler implored patients to ask questions. Ask your doctor questions about the treatment plan they create for you. Ask what component of MPN symptoms they are focusing on, and how the treatment they recommend will address that component (anemia, blood counts, spleen reduction, etc.). He stressed getting your COVID-19 vaccine and boosters. He also made clear that your questions matter and not to be afraid to ask.
We want to thank the specialists for sharing their valuable information and spending their time away from their respective institutions. We also want to thank our patients and their family members and friends for joining us and asking such thought-provoking questions. We hope that you will have a chance to join us at our next MPN Advocacy and Education International in-person event in Asheville, NC on Thursday August 22nd. To learn more, please visit www.mpnadvocacy.com/events-list.
Participants Discuss Treating a Patient With Myelofibrosis and Anemia
Targeted Oncology Staff
PARTICIPANT LIST Abhirami Vivekanandarajah, MD | Hayan Moualla, MD | Subhash C. Proothi, MD | Meher Burki, MD | Simi Masand Rai, MD | Rajesh Thirumaran, MD | Nirmala Nathan, MD
CASE SUMMARY
A 76-year-old woman presented to her physician with symptoms of mild fatigue, night sweats, and abdominal pain/fullness for 4 months; she also reported an unexplained weight loss of 12 lb. Her spleen was palpable 8 cm below the left costal margin. She had no known comorbidities.
Laboratory values included a red blood cell count of 3.40 × 106/μL, hemoglobin of 9.8 g/dL, and a platelet count of 181 × 103/μL. Next-generation sequencing showed a JAK2 V617F mutation. Her karyotype was 46,XX. A bone marrow biopsy showed megakaryocyte proliferation and atypia with evidence of reticulin fibrosis. The patient received a diagnosis of primary myelofibrosis with a high-risk result from the Dynamic International Prognostic Scoring System, an intermediate risk result from the Mutation-Enhanced International Prognostic Score System (MIPSS70), and a high risk result from the MIPSS70+ version 2.0.
Recombinant interferon alfa in BCR/ABL-negative chronic myeloproliferative neoplasms
1
Abstract
The treatment landscape for BCR/ABL-negative myeloproliferative neoplasms (MPNs), driven by JAK2, CALR, and MPL mutations, has evolved significantly over the last decade. Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. Many clinical trials have documented the safety and efficacy of IFN-α therapy in PV and essential thrombocythemia, the classical BCR/ABL-negative MPNs. Used off-label for more than 30 years as a cytoreductive agent, IFN-α therapy promotes significant clinical, hematologic, and molecular responses. In some IFN-α-treated patients, partial or complete reduction of the mutant JAK2 allele burden may lead to a durable measurable residual disease state, owing to the ability of long-term IFN-α therapy to selectively deplete mutant JAK2-harboring hematopoietic stem cells. Pegylated IFN-α forms were developed to improve the drug stability and tolerability of first-generation IFN-α therapeutics. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.