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Participants Discuss Treating a Patient With Myelofibrosis and Anemia

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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.

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Recombinant interferon alfa in BCR/ABL-negative chronic myeloproliferative neoplasms

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El Bitar S 1, Arcasoy MO 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.

MorphoSys Enters into Business Combination Agreement to be Acquired by Novartis for € 2.7 Billion Equity Value

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PLANEGG/MUNICH, Germany – February 5, 2024 – MorphoSys AG (FSE: MOR; NASDAQ: MOR) today announced the company entered into a Business Combination Agreement with Novartis data42 AG and Novartis AG (hereinafter collectively referred to as “Novartis”) based on Novartis’ intention to submit a voluntary public takeover offer for all outstanding MorphoSys no-par value bearer shares at an offer price of € 68.00 per share in cash. As part of the Business Combination Agreement with Novartis, Novartis seeks to obtain exclusive, worldwide rights to develop and commercialize pelabresib, an investigational BET inhibitor, and tulmimetostat, an investigational next-generation dual inhibitor of EZH2 and EZH1, across all indications. Separately, MorphoSys entered into a Purchase Agreement to sell and transfer all rights worldwide related to tafasitamab to Incyte Corporation (“Incyte”). Currently, MorphoSys partners with Incyte on the development and commercialization of tafasitamab. MorphoSys’ Management Board and Supervisory Board unanimously approved both agreements.

“Novartis shares our steadfast commitment to develop and deliver transformative medicines that address the dire needs of cancer patients. Pelabresib – the investigational therapy at the forefront of our promising oncology pipeline – has the potential to shift the treatment paradigm in myelofibrosis and further expand into other indications. Novartis will provide ample resources currently unavailable to MorphoSys as a standalone biotech company to help accelerate the development opportunities and maximize the commercialization potential of pelabresib at a greater speed and scale,” said Jean-Paul Kress, M.D., Chief Executive Officer of MorphoSys. “We are also pleased that Incyte will assume full responsibility of tafasitamab. Given the proposed acquisition by Novartis and our long-standing partnership with Incyte, we know Incyte is best positioned to drive tafasitamab’s future growth opportunities forward successfully and more efficiently on its own at this time. We believe these agreements are in the best interest of MorphoSys, our shareholders and cancer patients.”

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Preliminary data shows lowered cytokine levels in myelofibrosis with PIM1 kinase inhibitor

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December 19, 2023

SAN DIEGO — Treatment with a selective PIM1 kinase inhibitor showed positive clinical reactions in a sample of 23 patients with relapsed/refractory myelofibrosis, according to preliminary data presented at ASH Annual Meeting.

TP-3654, an oral investigational highly selective PIM1 kinase inhibitor, is the subject of the phase 1/phase 2 study evaluating monotherapy in relapsed/refractory myelofibrosis, according to results published by a team led by Lindsay A.M. Rein, MD, a hematologic oncologist at Duke Cancer Center.

Elevated circulating cytokines have previously been noted as having a strong association with myelofibrosis, and preclinical studies evaluating TP-3654 as both a monotherapy and in tandem with ruxolitinib (Jakafi, Incyte) displayed lowered cytokine response and other responses, such as spleen reduction and bone marrow fibrosis reduction.

As such, the phase 1/phase 2 study further examined TP-3654 monotherapy in a cohort of patients with intermediate or high-risk myelofibrosis, and who had been previously treated with or were ineligible for JAK inhibitor treatment.

The 23 patients — who had a median age of 73 years and all but one of whom had previously received JAK inhibitor treatment — were monitored for cytokine changes over 12 weeks of TP-3654 monotherapy. “Broad reductions” in cytokine levels were observed in as little as 24 hours, and over the course of 12 weeks, patients with higher cytokine reduction levels were found to have greater reduction in symptoms.

Twelve of 13 eligible patients saw a reduction in their total symptom score, with seven having their score reduced by 50% or more. Treatment-related adverse events, such as nausea and vomiting, were observed in over 20% of patients.

Rein noted that enrollment is still ongoing.

Reference:

Rein LAM, et al. Phase 1/2 study of TP-3654, a selective PIM1 kinase inhibitor: Preliminary data showed clinical activity and cytokine reductions in relapsed/refractory myelofibrosis patients. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2023; San Diego.

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MPN-Associated Anemia: What Nurses Should Look Out For

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Sharon Bledsoe, MSN, MBA, BSN, RN

When treating patients with blood cancers such as myeloproliferative neoplasms (MPNs), it is essential for oncology nurses to explain to patients what to expect and what symptoms they should call about. And when the patients talk, it is essential that their nurses are attentive, explained Sharon Bledsoe, MSN, MBA, BSN, RN.

“Make sure that you listen to your patient and that you absolutely follow up with all of their labs and watch and monitor their trends,” Bledsoe, a senior research nurse at The University of Texas MD Anderson Cancer Center, said in an interview with Oncology Nursing News®.

In the case of myelofibrosis (a type of MPN), patients may experience a slow downward trend in hemoglobin levels, as the bone marrow scarring inhibits the body’s ability to produce healthy red blood cells. In turn, patients end up developing anemia. Patients with myelofibrosis-associated anemia may experience a change in their typical MPN-related symptoms, increased fatigue, night sweats, or fever, according to Bledsoe.

However, decreases in blood levels for patients with myelofibrosis may not be as sharp or apparent for patients with myelofibrosis as they are for other malignancies, such as acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), Bledsoe explained.

“It’s a slow trend. It’s not usually a sudden trend when you’re dealing with myelofibrosis, and it can progress slower than ALL or AML or any of those other blood cancers,” she said.

While the trend may be slow, it is important to catch anemia quickly, according to Bledsoe, so that treatments — namely blood transfusions or JAK inhibitors — can be started in a timely manner and ensure the best outcome for the patient.

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Socio-Racial Factors May Impact Primary Myelofibrosis Outcomes

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Russ Conroy

Mohammad Bakri Hammami, MD, highlights a need to address socio-racial disparities among Black and non-Black patients with primary myelofibrosis to ensure that everyone receives high-quality treatment.

Investigators retrospectively reviewed socio-racial characteristics as potential determinants of survival in patients with primary myelofibrosis and compared the dataset with single-center outcomes of patients treated at Montefiore Medical Center.

Investigators identified that certain socio-racial factors, including race, sex, and age, may potentially affect survival outcomes in patients with primary myelofibrosis, according to data from a retrospective review that were presented at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting.

Data collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020 highlighted a median overall survival (OS) of 47 months in the overall population with primary myelofibrosis. Additionally, investigators reported an estimated OS rate of 69% at 2 years and 41% at 5 years.

According to presenting author Mohammad Bakri Hammami, MD, an internal medicine resident at Albert Einstein College of Medicine and Jacobi Medical Center, patient age significantly correlated with OS (HR, 1.042; 95% CI, 1.038-1.046; P <.001) in the SEER cohort. Additionally, investigators observed statistically significant worse OS outcomes in male patients compared with their female counterparts (HR, 1.399; 95% CI, 1.277-1.533; P <.001), as well as in Black patients compared with non-Black patients (HR, 1.202; 95% CI, 1.016-1.422; P <.032).

Hammami noted that patients pulled from the SEER database who were diagnosed with primary myelofibrosis after 2011 experienced significantly better survival with respect to cause-specific and all-cause mortality (P = .001). Being married was also a protective factor against all-cause mortality (P = .001).

In a cohort of patients with primary myelofibrosis treated at Montefiore Medical Center, the 2-year and 5-year OS rates, respectively, were 92% and 63%. The most common treatment modalities administered to Black and non-Black patients in the Montefiore cohort, respectively, included ruxolitinib (Jakafi; 50.0% and 43.9%), hydroxyurea (20.0% and 19.5%), and fedratinib (Inrebic; 10.0% and 0.0%). Additionally, 10.0% of Black patients and 14.6% of non-Black patients were treated as part of a clinical trial. Overall, Hammami stated that there were “no real differences” in the rates of treatment modalities between Black and non-Black patients treated at Montefiore.

In an analysis of genetic mutations in patients receiving treatment at Montefiore, Black and non-Black patients, respectively, typically had JAK2 (70% and 78%), CALR (20% and 16%), and ASXL1 (40% and 5%) mutations. According to Hammami, there was a generally similar distribution of genetic mutations in patients regardless of race, which was consistent with prior reports.

“There is a real role for social factors in terms of survival, especially when it comes to Black and non-Black patients,” Hammami said. “There is a need to focus on addressing these factors when we want to provide high-quality care to these patients.”

Investigators retrospectively reviewed socio-racial characteristics as potential determinants of survival in patients with primary myelofibrosis and compared the dataset with single-center outcomes of patients treated at Montefiore Medical Center. Patients with no histological confirmation of disease or active follow up were not included in the analysis. Additionally, investigators assessed medical records from patients treated at Montefiore Medical Center from 2007 to 2023.

Across the 17 SEER registries, investigators assessed data from 5403 patients. The overall population consisted of patients who were White (82.0%), Black (8.4%), and Asian or from the Pacific Islands (7.7%).

Among non-Black and Black patients included in the SEER cohort, respectively, the mean age was 69 years and 64 years (P <.001); most patients were male (60.7% vs 52.1%; P <.001). Additionally, the majority of non-Black patients were married (57.4%), whereas most Black patients were unmarried (63.4%; P <.001). Hammami also highlighted that 55.0% of non-Black patients had an annual income of over $70,000, while 59.6% of Black patients earned less than $70,000 per year.

The Montefiore cohort consisted of 51 patients, including 43 who were censored and 8 who died due to cancer. Additionally, 57% of patients were male, and 49% were married. The median patient age in this cohort was 66 years. The Montefiore population consisted of patients who were White (35%), Black (20%), Asian (10%), or another or unknown race (35%).

Reference

Hammami MB, Yang J, Thakur R, et al. Examining racial disparities in the incidence and survival of myelofibrosis: insights from SEER database and an institutional cohort (2000-2020). Presented at: 2023 Society of Hematologic Oncology (SOHO). Annual Meeting; September 6-9, 2023; Houston, TX. Abstract MPN-470.

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Scientists create a tool to identify individuals at risk of developing different myeloid leukemias

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August 24, 2023

by Wellcome-MRC Cambridge Stem Cell Institute

Scientists have created a new test for identifying people at risk of developing acute myeloid leukemia and related cancers, years before they do. The new platform, “MN-predict,” will allow doctors and scientists to identify those at risk and to design new treatments to prevent them from developing these potentially lethal cancers.

Researchers at the Wellcome-MRC Cambridge Stem Cell Institute (CSCI), the University of Cambridge’s Department of Haematology, and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA) analyzed data from more than 400,000 individuals participating in the United Kingdom Biobank.

Using this data, the scientists have created “MN-predict,” a platform for predicting the risk of developing blood cancers such as acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms over a 10–15-year period.

This test, now available in NHS clinics, requires patients to provide a blood sample from which DNA is extracted for limited sequencing, alongside basic blood cell counts. With this information, MN-predict identifies those at high risk of any of these cancers and can be used in specialist clinics for leukemia prevention.

Professor George Vassiliou, senior author of the study said, “We all know that prevention is better than cure, but it is not easy to prevent diseases like leukemia without knowing who is at risk. MN-predict makes it possible to identify at-risk individuals, and we hope it can become an essential part of future leukemia prevention programs.”

The myeloid neoplasms are a group of related cancers encompassing acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Treatments for these cancers have improved in the last few years, but most cases remain incurable.

In the last few years, scientists discovered that these cancers develop over decades through the accumulation of DNA mutations in blood stem cells, the cells responsible for normal blood formation. These mutations encourage these stem cells to grow faster than normal and, as more mutations accumulate, they can progress towards leukemia.

Thankfully, while mutations that promote cell growth are common, leukemia develops only in a small minority of cases. Identifying these cases early on helps efforts to prevent the cancers from developing.

Dr. Muxin Gu, first author of the paper, said, “We hope that MN-predict will help clinicians to identify people at risk of myeloid cancers and use novel treatment to prevent the cancers from developing.”

Dr. Pedro M. Quiros, joint senior author of the study, said, “Despite some recent advances in their treatment, these cancers remain lethal to many sufferers. We hope that our efforts will help advance prevention in favor of treating the full-blown disease.”

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Ajax Therapeutics Appoints Dr. David Steensma as Chief Medical Officer

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– A leading expert in hematologic malignancies with more than 25 years of oncology clinical and research experience, Dr. Steensma joins Ajax as its lead JAK2 inhibitor advances to the clinic –

NEW YORK–(BUSINESS WIRE)–Ajax Therapeutics, Inc., a biopharmaceutical company applying computational chemistry and structure-based technologies to develop next generation JAK inhibitors for patients with myeloproliferative neoplasms (MPNs), today announced the appointment of David P. Steensma, MD, FACP, as Chief Medical Officer. A renowned expert in hematologic malignancies, Dr. Steensma was formerly the Global Head of Hematology at Novartis Institutes for Biomedical Research, where he led early clinical development in malignant and non-malignant hematology conditions.

“His deep knowledge of hematologic malignancies and extensive experience leading clinical studies will be invaluable as we prepare to enter our first in human studies in myelofibrosis in 1H 2024.”

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“We are very fortunate to have such a veteran hematology drug developer as David join the Ajax team as we near the clinic with our next generation Type II JAK2 inhibitor program for MPNs,” said Martin Vogelbaum, CEO of Ajax Therapeutics. “His deep knowledge of hematologic malignancies and extensive experience leading clinical studies will be invaluable as we prepare to enter our first in human studies in myelofibrosis in 1H 2024.”

“I have collaborated with David for many years and consider him one of the top thought leaders in hematology oncology,” said Dr. Ross Levine, Chair of Ajax’s SAB and Deputy Physician-in-Chief, Translational Research, Laurence Joseph Dineen Chair in Leukemia Research and Member of the Human Oncology and Pathogenesis Program at Memorial Sloan Kettering Cancer Center. “We are very pleased to have David on board as his unique combination of translational and clinical skills will help us effectively design and execute clinical studies to demonstrate the unique and differentiating clinical properties of our lead Type II JAK2 inhibitor program.”

“I am excited to join Ajax at this pivotal stage of the company’s development,” said Dr. Steensma. “Patients with MPNs continue to have major unmet clinical needs as current therapies, including approved JAK inhibitors, such as ruxolitinib, often fail to provide adequate symptomatic relief and have no effect on the course of their disease. Ajax’s Type II JAK inhibitor is a more selective and potent JAK inhibitor with the potential to significantly improve efficacy, overcome disease persistence and, more importantly, provide disease modification.”

Dr. Steensma has a more than 25-year distinguished career as a clinician, investigator and researcher in hematology-oncology. Prior to his R&D leadership role at Novartis Institutes for Biomedical Research, he was a faculty member at Harvard Medical School and Institute Physician in the Adult Leukemia Program in the Division of Hematological Malignancies at the Dana-Farber Cancer Institute, where he cared for patients with hematological malignancies and bone marrow failure and served as the Edward P. Evans Chair in Myelodysplastic Syndromes (MDS). Earlier in his career, Dr. Steensma was a fellow and then faculty member in the Division of Hematology, Department of Medicine, at the Mayo Clinic. Since 2000, he has been on numerous committees and held several editorial roles for the American Society of Hematology and served as consultant editor for the Journal of Clinical Oncology. He was also a voting member of the Oncology Drug Advisory Committee (ODAC) for the U.S. Food and Drug Administration (FDA), and member of the Board of Directors of the MDS Foundation. Dr. Steensma has published over 200 original research papers as well as numerous reviews, editorials and book chapters. He received his medical degree from the University of Chicago’s Pritzker School of Medicine.

About Ajax Therapeutics

Ajax Therapeutics, Inc. is pursuing uniquely selective approaches to develop novel next generation JAK2 therapies for myeloproliferative neoplasms (MPNs), including myelofibrosis. By combining the deep cancer and structural biology insights of our founding scientists with the industry’s most advanced computational drug discovery and protein structure platforms from our founding partner, Schrödinger, Inc., we aim to discover and develop more precisely designed therapies to address the significant unmet needs for patients with MPNs.

Please find more information at www.ajaxtherapeutics.com.

NOTE: Dr. Ross Levine serves on the board of directors of, has provided advisory services for, and has equity interests in Ajax Therapeutics. Dr. Levine also has intellectual property rights and interests that MSK has licensed to Ajax. MSK has intellectual property rights and other financial interests related to Ajax.

Lindsey Lyle on Differentiating MPN Symptoms From Other Health Issues

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June 30, 2023

Lindsay Lyle, PA-C, MS

It can often be difficult for oncology nurses and other clinicians to determine if a patient’s symptoms are related to their myeloproliferative neoplasm (MPN) or another underlying cause, making a detailed medical history extremely important, explained Lindsey Lyle, PA-C, MS, a nurse practitioner who specializes in hematologic malignancies.

“This is a big challenge for nurses, advanced practice providers and physicians alike,” Lyle said in an interview with Oncology Nursing News®.

Common MPN symptoms — including fatigue, bone aches and pains, night sweats, unintentional weight loss, rib pain and feeling full after eating small amounts of food — are relatively broad and can be associated with numerous health conditions, Lyle said, noting that it is important to rule out other possible causes.

To ensure that these symptoms are not related to another cause, nurses must ask patients about their past medical history, other health conditions, changes in medications, and timing of symptoms. Lyle noted that the patient’s primary care physician can also be a good source of information regarding the timing of a patient’s symptoms.

“When a patient does have a diagnosis of an MPN, we certainly can assume that maybe it is the MPN until other contributors have been ruled out,” Lyle said. “So timing of these symptoms is really important; a nurse can ask about when symptoms first started, what they were doing when these symptoms happened and what makes them better, or what makes them worse.”

Additionally, Lyle mentioned that nurses should ask patients about how treatments change their symptoms, as some drugs that are currently used to treat MPNs — such as the JAK inhibitors ruxolitinib (Jakafi), fedratinib (Inrebic), and pacritinib (Vonjo) — can decrease symptoms, such as splenomegaly. In fact, last year, the Food and Drug Administration (FDA) approved pacritinib for patients with intermediate- or high-risk primary or secondary myelofibrosis because the phase III PERSIST-2 trial showed that the drug decreased spleen volume by at least 35% in 29% of patients.1

Reference

  1. Mascarenhas J, Hoffman R, Talpaz M, et al. Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol. 2018;4(5):652-659. doi:10.1001/jamaoncol.2017.5818

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Rusfertide Offers Durable Hematocrit Control in Phlebotomy-Dependent Polycythemia Vera

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June 11, 2023

Caroline Seymour

Rusfertide (PTG-300) demonstrated freedom from phlebotomy, sustained hematocrit control, and 12-week treatment completion in 69.2% (n = 18/26) vs 18.5% (n = 5/27) of patients with phlebotomy-dependent polycythemia vera who received placebo (P = .0003), meeting the primary end point of the phase 2 REVIVE trial (NCT04057040). Findings were presented at the 2023 EHA Congress.

“The REVIVE study demonstrated significantly higher efficacy with rusfertide compared with placebo in subjects with polycythemia vera,” said Marina Kremyanskaya, MD, PhD, lead study author and assistant professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York, New York, in a presentation of the data. “Current standard-of-care therapy in polycythemia vera does not consistently maintain hematocrit below 45%, thereby potentially increasing the risk of thromboembolic events. Rusfertide has the potential to consistently maintain hematocrit [levels] below 45%.”

Polycythemia vera is a myeloproliferative neoplasm (MPN) that produces red blood cells in excess and is often marked by elevated hematocrit. Hematocrit, when uncontrolled, can lead to higher fatality from cardiovascular causes or thrombotic events. Although guidelines from the National Comprehensive Cancer Network and European LeukemiaNet state that hematocrit should be maintained below 45%, current standard-of-care therapy fails to do so in most patients.

Hepcidin is a peptide hormone that controls iron availability for red blood cell formation. Rusfertide is a novel hepcidin mimetic that mirrors the effects of hepcidin on erythropoiesis, representing a potential add-on therapy to standard therapy with improved activity. This hypothesis was tested in the phase 2 REVIVE trial.

To be eligible for enrollment in the study, patients had to have phlebotomy-dependent polycythemia vera per 2016 World Health Organization criteria, having received at least 3 phlebotomies in 28 weeks with or without concurrent cytoreductive therapy. Additionally, all patients had to be phlebotomized to hematocrit levels below 45% prior to the first dose of rusfertide to standardize the starting hematocrit.

The study consisted of 3 parts: dose finding, blinded randomized withdrawal, and open-label extension. Rusfertide was administered subcutaneously in doses ranging from 10 mg to 120 mg weekly. In part 1, rusfertide was titrated for the first 16 weeks to determine the clinically effective dose. Efficacy was evaluated in weeks 17 to 28. In part 2, patients were randomly assigned 1:1 to receive active or placebo doses of rusfertide in weeks 29 to 41. Study treatment continued in part 3 for up to 3 years.

Safety and efficacy served as key end points of the trial. Efficacy was characterized by the proportion of responders in part 2, defined by the proportion of patients who maintained hematocrit below 45% and the percentage reduction in phlebotomies. Patient outcomes were evaluated with the MPN Symptoms Assessment Form Total Symptom Score.

A total of 70 patients were included in the dose-finding portion of the research. Fifty-nine patients were treated in part 2, 53 of which were included in the primary efficacy analysis set. Fifty-two patients are ongoing treatment in part 3

Regarding baseline characteristics of those included in part 2, most patients were male, above the age of 50 years at diagnosis, had polycythemia vera for approximately 5 years, and received hydroxyurea as the primary means of cytoreductive therapy. Across the arms, 52.7% of patients were high risk and 47.4% were low risk. Body mass index was 30.1 ± 5.76 kg/m2 and 28.7 ± 4.55 kg/m2 in the placebo and rusfertide arms, respectively.

Additional findings demonstrated similar benefit in time to treatment failure with rusfertide in responders (P < .0001), patients ineligible for phlebotomy plus hydroxyurea (P < .0001), and those with hematocrit under 45% (P < .0001).

Kremyanskaya also explained that rusfertide led to meaningful reductions in the need for phlebotomy, both with phlebotomy only (n = 37) and phlebotomy plus cytoreductive therapy (n = 33).

Although the focus of the presentation centered around outcomes in part 2, investigators also evaluated symptom improvement in part 1. Notably, moderate or severe symptoms of problems with concentration (P =.0018), itching (P = .0054), fatigue (P =.0074), and inactivity (P =.0005) were all improved following treatment with rusfertide. Kremyanskaya noted that meaningful comparison of symptom improvement was not possible in part 2 because most patients who were randomized to placebo discontinued prior to the 12-week symptom assessment.

In terms of safety, Kremyanskaya stated that rusfertide was “generally well tolerated.” Treatment-emergent adverse effects (TEAEs) included injection site erythema (64.3%), injection site pain (41.4%), injection site pruritus (40.4%), fatigue (31.4%), injection site mass (25.7%), pruritus (25.7%), arthralgia (24.3%), injection site swelling (24.3%), dizziness (22.9%), headache (22.9%), nausea (22.9%), anemia (20.0%), COVID-19 (20.0%), injection site irritation (18.6%), and injection site bruising (15.7%). Most events were grade 1/2 (83%), and 17% of patients experienced grade 3 events. No grade 5 events occurred.

“Most common TEAEs were injection site reactions, which decreased in incidence with continued treatment,” Kremyanskaya noted. “Additionally, events were localized, grade 1 or 2 in severity, and generally did not lead to treatment discontinuation,”

Two treatment-related events of mild thrombocytosis and recurrent grade 1 injection site erythema led to treatment discontinuation.

Patients who completed the REVIVE study will be eligible to enroll in PTG-300-21, a separate, 2-year follow-on extension trial. The agent is also under evaluation in the phase 3 VERIFY trial (NCT05210790), where it is being compared with placebo in patients with polycythemia vera maintaining hematocrit control and in improving symptoms of disease.

Disclosures: Dr Kremyanskaya reported receiving honoraria and being on the advisory board for Protagonist Therapeutics, Inc.

Reference

Kremyanskaya M, Kuykendall A, Pemmaraju N, et al. Targeted therapy of uncontrolled erythrocytosis in polycythemia vera with the hepcidin mimetic, rusfertide: – blinded randomized withdrawal results of the REVIVE study. Presented at: 2023 EHA Congress; June 8-11, 2023; Frankfurt, Germany. Abstract LBA2710.

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