Tag Archives: polycythemia vera

A Grand Time in Grand Rapids

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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.

Dr Raajit Rampal Discusses Disease Modification and Emerging Therapies in Polycythemia Vera

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Laura Joszt, MA

Achieving a disease-modifying therapy for polycythemia vera might require adjusting the end points in a study needed for a drug to be approved, said Raajit Rampal, MD, PhD, hematologic oncologist, associate attending physician, Memorial Sloan Kettering Cancer Center.

Transcript

Currently, there are no disease-modifying treatments in polycythemia vera, but it is being explored. What might such a therapy look like?

If we talk about disease modification, the first question is, what do you mean by disease modification? I think, what we would want is for our patients to live the longest and fullest life, free of the symptoms or burdens of their disease. To me, that is the sort of working definition of disease modification. From there, one can try to come up with biological definitions of things like depleting the stem cell, which are important things. But keeping this on a patient level, what we want for our patients [is a life free of disease burden]. How do we think about therapies that address those issues?

Part of it is a regulatory conundrum in the sense that studies have to meet certain end points for drugs to get approved, but the way we study the drugs is relative to the definitions of the end points that make the drugs successful. In many cases, [the end point is asking] are you controlling the hematocrit adequately? That’s one of the major things in polycythemia vera. But in order to really try to get at the question of disease modification, we’ve got to think about changing the end points of our studies to reflect that.

What are the things that are going to best correlate with the idea that you aren’t keeping patients free of the catastrophic consequences of their disease, like blood clots, like [disease] turning into leukemia or myelofibrosis? Are you controlling the patient’s symptoms to an adequate degree? Those are the things that I think are fundamental. But we’ve got to change the end points of our studies to really get at that.

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Younger Patients With PV May Benefit From Earlier Treatment With Cytoreductive Therapies

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Laura Joszt, MA

Although patients younger than age 60 with polycythemia vera (PV) are typically not treated with cytoreductive therapy due to treatment toxicity concerns, this may result in an undertreatment of patients as there is no clear evidence that the risk of toxicity exceeds the potential benefit of treatment, according to a study published in Blood Advances.1

PV causes an overproduction of blood cells in the bone marrow, which leads to high numbers of circulating red blood cells.2 This thickens the blood, which may not flow through smaller blood vessels properly. Although PV can be diagnosed at any age, it most often occurs in people over the age of 60 years.2

For most patients, phlebotomy is the standard treatment, and it may be the only treatment needed for years. However, additional treatment to suppress the formation of blood cells in the bone marrow may be needed. Cytoreductive therapies, such as interferons, hydroxyurea, ruxolitinib, and anagrelide, may be needed, particularly for high-risk patients.3

Currently, cytoreductive therapies are not routinely recommended by the European LeukemiaNet or National Comprehensive Cancer Network for patients with PV younger than 60 years who don’t have a history of thrombosis, a high symptom burden, or an intolerance to phlebotomy.

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Rusfertide Treatment Strengthens Response and Decreases Erythrocytosis Among Patients With Polycythemia Vera

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Jordan Kadish

03/22/2024

According to findings from the international phase 2 REVIVE trial published in The New England Journal of Medicine, treatment with rusfertide, a peptide mimetic of the master iron regulatory hormone hepcidin, strengthened responses and decreased erythrocytosis among patients with polycythemia vera (PV). Patients who received rusfertide demonstrated a mean hematocrit of less than 45% during the dose-finding period.

Marina Kremyanskaya, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, New York, and coauthors stated, “Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis,” or a high concentration of red blood cells in the blood. “The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown,” they added.

To expand on the available research, the study authors aimed to assess the efficacy of rusfertide among patients with polycythemia vera. The primary end point was a response, which was characterized by the hematocrit control, absence of phlebotomy, and finishing the trial regimen during part 2. The modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary was utilized to assess patient-reported outcomes of symptoms.

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Disease-, Age-, Genomic-Specific Factors Increase Risk of ET, PV, PrePMF Developing Into Overt MF

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Laura Joszt, MA

The risk of essential thrombocytopenia (ET), polycythemia vera (PV), and prefibrotic primary myelofibrosis (PrePMF) developing into overt myelofibrosis (MF) increases with age, the accumulation of mutations, and the activation of proliferative pathways, which identifies new targets for therapeutic intervention.

The findings, based on an analysis of the mutational landscape of more than 1700 genes and the gene expression of various cells from patients with myeloproliferative neoplasms (MPNs), was published in Clinical Cancer Research.1

ET, PV, PMF, and MF are all part of a group of diseases MPNs, in which a mutation in the bone marrow causes too many red blood cells, white blood cells, or platelets.2 In addition to being the most common MPNs, ET, PV, and PMF share the presence of mutations in either Janus kinase 2 (JAK2), calreticulin (CALR), and/or MPL.3 ET and PV are less aggressive forms of MPN, but they still can progress to MF. According to the Leukemia & Lymphoma Society, Pre-PMF will likely progress to PMF, “suggesting that more regular observations for pre-fibrotic PMF patients is warranted.”3

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Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera

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Marina Kremyanskaya, M.D., Ph.D., Andrew T. Kuykendall, M.D., Naveen Pemmaraju, M.D., Ellen K. Ritchie, M.D., Jason Gotlib, M.D., Aaron Gerds, M.D., Jeanne Palmer, M.D., Kristen Pettit, M.D., Uttam K. Nath, M.D., Abdulraheem Yacoub, M.D., Arturo Molina, M.D., Samuel R. Saks, M.D., et al., for the REVIVE Trial Investigators*

Abstract

BACKGROUND

Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.

METHODS

 

In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).

RESULTS

Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P=0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.

CONCLUSIONS

In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040. opens in new tab.)

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Rusfertide Improves Responses in Phlebotomy-Dependent Polycythemia Vera

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Caroline Seymour

Patients with phlebotomy-dependent polycythemia vera, a type of myeloproliferative neoplasm, treated with rusfertide experienced a response rate of 60% (n = 18/30) compared with 17% (n = 5/29) in those who received placebo (P = .002), according to updated findings from part 2 of the phase 2 REVIVE trial (NCT04057040) published in the New England Journal of Medicine.1

The international trial was designed with 3 parts: a 28-week, open-label, dose-finding portion in which rusfertide was added to a patient’s ongoing therapy of phlebotomy alone or cytoreductive therapy with optional phlebotomy; a double-blind, randomized withdrawal portion wherein patients were randomly assigned to receive rusfertide or placebo for 12 weeks (weeks 29 to 41); and an open-label extension period following patients on rusfertide therapy for up to 3 years.

Findings from part 1 showed that the estimated mean number of annual phlebotomies was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). Moreover, the mean maximum hematocrit level was 44.5±2.2% during part 1 vs 50.0±5.8% during the 28 weeks before the first dose of rusfertide. Patient quality of life was also improved on rusfertide, with a lower severity of disease-related symptoms.

“Rusfertide appears to represent a significant step forward in treating [patients with] polycythemia vera through its unique approach of limiting the amount of iron available for blood cell production,” Marina Kremyanskaya, MD, PhD, an associate professor of medicine (hematology and medical oncology) at Icahn School of Medicine at Mount Sinai in New York, New York, and lead author of the study, stated in a news release.2 “Pending further clinical studies, this injectable agent could become a valuable therapeutic tool for a disease which many patients and their physicians struggle to bring under control.”

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Rusfertide More Than Triples Responses Vs Placebo in Phlebotomy-Dependent Polycythemia Vera

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Caroline Seymour

Treatment with rusfertide led to a 60% response rate (n = 18/30) vs 17% (n = 5/29) with placebo in patients with phlebotomy-dependent polycythemia vera (P = .002), according to updated findings from part 2 of the phase 2 REVIVE trial (NCT04057040) which were published in the New England Journal of Medicine.1

The international trial was designed with 3 parts: a 28-week, open-label, dose-finding portion in which rusfertide was added to a patient’s ongoing therapy of phlebotomy alone or cytoreductive therapy with optional phlebotomy; a double-blind, randomized withdrawal portion wherein patients were randomly assigned to receive rusfertide or placebo for 12 weeks (weeks 29 to 41); and an open-label extension period following patients on rusfertide therapy for up to 3 years.

Findings from part 1 showed that the estimated mean number of annual phlebotomies was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). Moreover, the mean maximum hematocrit level was 44.5±2.2% during part 1 vs 50.0±5.8% during the 28 weeks before the first dose of rusfertide. Patient quality of life was also improved on rusfertide, with a lower severity of disease-related symptoms.

“Rusfertide appears to represent a significant step forward in treating [patients with] polycythemia vera through its unique approach of limiting the amount of iron available for blood cell production,” Marina Kremyanskaya, MD, PhD, an associate professor of medicine (hematology and medical oncology) at Icahn School of Medicine at Mount Sinai in New York, New York, and lead author of the study, stated in a news release.2 “Pending further clinical studies, this injectable agent could become a valuable therapeutic tool for a disease which many patients and their physicians struggle to bring under control.”

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PharmaEssentia’s BESREMi (ropeginterferon alfa-2b-njft) Now Recommended as a Preferred First-line Cytoreductive Therapy for Polycythemia Vera in Updated NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)

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Update based on NCCN’s determination of superior efficacy, safety and evidence for BESREMi in high and low-risk patients, reflecting an ongoing shift in PV care toward earlier intervention

BURLINGTON, Mass.–(BUSINESS WIRE)–PharmaEssentia USA Corporation, a subsidiary of PharmaEssentia Corporation (TWSE: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) have recently been updated to include ropeginterferon alfa-2b-njft, marketed as BESREMi®, as a preferred first-line cytoreductive therapy option for the treatment of adults with symptomatic, low-risk polycythemia vera (PV). Ropeginterferon alfa-2b-njft is the only preferred therapeutic option for both high-risk and low-risk (symptomatic) PV regardless of treatment history.1

“The recent update to the NCCN Guidelines® reflects the ongoing shift in PV care towards earlier intervention, focusing on long-term patient health,” said Rami Komrokji, M.D., Vice Chair of the Malignant Hematology Department and Head of the Leukemia and MDS Section at Moffitt Cancer Center.

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Study shows early success of a novel drug in treating a rare and chronic blood cancer

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February 21, 2024

by The Mount Sinai Hospital

A novel treatment for polycythemia vera, a potentially fatal blood cancer, demonstrated the ability to control overproduction of red blood cells, the hallmark of this malignancy and many of its debilitating symptoms in a multi-center clinical trial led by the Icahn School of Medicine at Mount Sinai.

In the phase 2 study, the drug rusfertide limited excess production of red blood cells, the main manifestation of polycythemia vera, over the 28-week course of treatment. The results suggest it could replace therapeutic phlebotomy, a common form of treatment which has proven to be a burden for many patients. The results of the study were published today (Feb. 21) in The New England Journal of Medicine.

“Rusfertide appears to represent a significant step forward in treating polycythemia vera through its unique approach of limiting the amount of iron available for blood cell production,” says Marina Kremyanskaya, MD, Ph.D., Associate Professor of Medicine (Hematology and Medical Oncology) at Icahn Mount Sinai and lead author of the study.

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