Tag Archives: mpn

New Model Can Assess Blast Phase Progression Risk in Myeloproliferative Neoplasms

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November 12, 2024

Author(s): Alexandra Gerlach, Associate Editor

Researchers from Germany developed a model that utilizes 12 genetic markers to accurately distinguish patients with varying myeloproliferative neoplasms (MPNs) including chronic myeloid leukemia (CML) and BCR::ABL1 negative MPNs polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). Using the model, clinicians can more precisely characterize their disease and determine their risk of progression to blast phase (BP).

Red blood cells and DNA strand | Image Credit: © GustavsMD – stock.adobe.com

MPNs are clonal disorders of the blood cells and bone marrow characterized by abnormal hematopoietic proliferation, which have been differentiated into 8 subclasses by the World Health Organization. However, the 4 classical types are CML, PV, PMF, and ET, characterized by mutations in the JAK2, CALR, or MPL driver genes.1,2

Diagnosis of a specific MPN is based on their unique morphology; for example, PV is distinguished by a hypercellular bone marrow and elevated hemoglobin level, compared with ET, which is characterized by megakaryocytic proliferation and increased platelet counts. However, this approach fails to acknowledge overlaps, borderline findings, or potential transitions to other MPN subtypes. Patients with PV and patients with ET can progress to post-PV or post-ET myelofibrosis (MF), underscoring the genetic intricacy of these disorders. There is also the risk of progression to BP, also called leukemic transformation, in which the presence of circulating or bone marrow blasts is ≥20%.2-4

In the study, the researchers aimed to use genetic markers to more effectively stratify CML, PV, PMF, and ET, as well as characterize patients with progression to BP. They developed a machine-learning model based on 12 genetic markers observed in routine analysis to accurately classify MPN subtypes and provide useful prognostic information in a user-friendly decision tree format for clinicians. Using data from over 500 patients, they were able to genetically characterize 355 individuals with 1 of the 4 classic MPNs.1

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Lower Pharmacy Costs Give Ruxolitinib Edge for Patients With MF and Anemia

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November 9, 2024

Author(s): Mary Caffrey

The clinical benefits and lower transfusion costs of momelotinib (Ojjaara) are not enough to offset its higher pharmacy costs compared with an older therapy for patients with myelofibrosis (MF) and anemia who rely on transfusions, according to a recent cost-effectiveness analysis.

The results were presented in a poster at the 16th International Congress on Myeloproliferative Neoplasms, held in Brooklyn, New York, October 24-25, 2024.1

Aaron T. Gerds, MD, MS | Image Credit: Cleveland Clinic

Led by Aaron T. Gerds, MD, MS, assistant professor of Medicine, Cleveland Clinic Taussig Cancer Institute, the authors presented data based on a predictive model that computed per-patient total cost of care for 6-month, 1-year, and 2-year periods, comparing the Janus kinase (JAK) inhibitors ruxolitinib (Jakafi), and momelotinib (Ojjaara). Both inhibit the JAK/STAT pathway, with momelotinib additionally targeting a pathway that can result in improved iron-restricted anemia.

As the poster authors stated, ruxolitinib is indicated for patients with intermediate- or high-risk MF, including those with primary MF, post-polycythemia vera MF, post–essential thrombocythemia MF. Momelotinib is indicated for patients with intermediate- or high-risk MF, including those with primary MF, post-polycythemia vera MF, and post–essential thrombocythemia MF in in adult patients with anemia.1

The SIMPLIFY-2 study showed that patients switching from ruxolitinib to momelotinib took less time to achieve transfusion in dependence.2

This analysis presented in Brooklyn was based on the SIMPLIFY-1 study, which compared ruxolitinib and momelotinib in patients who had not previously received a JAK inhibitor.3 The authors, many of whom worked SIMPLIFY-1, found that the difference in pharmacy costs is $11,095 per month, with momelotinib being more expensive. Although transfusion costs for ruxolitinib were projected to cost an additional $10,854 over a 6-month period, the total cost of care still favored ruxolitinib, Results were as follows:

  • At the 6-month mark, the total cost of care favored ruxolitinib by$46,388.
  • At the 1-year mark, the total cost of care favored ruxolitinib by $84,239.
  • At the 2-year mark, the total cost of care favored ruxolitinib by $144,539.

Assumptions in the model. Authors wrote that the model assumed patients remained on therapy for the entire duration of the study or until death. It was limited to pharmacy- and transfusion-related costs, “to isolate costs associated with reductions in transfusion; other costs of care were assumed similar between ruxolitinib and momelotinib.”

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Ruxolitinib Provides Better Efficacy Than Best Available Therapy in Polycythemia Vera

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Andrea S. Blevins Primeau, PhD, MBA
According to the results of a systematic review and meta-analysis published in the journal APMIS, patients with polycythemia vera (PV) achieved greater hematocrit control and improved symptoms with ruxolitinib compared with best available therapy (BAT). Ruxolitinib was also associated with higher rates of nonmelanoma skin cancer, anemia, and certain infections.

Researchers identified 6 studies, including 4 randomized controlled trials and 2 observational studies, comprising 1061 patients with PV during the systematic review of reports published through 2023. The meta-analyses used a risk ratio (RR) to estimate effect size.

All patients received treatment with ruxolitinib or BAT, which included hydroxyurea, interferon, pegylated interferon, pipobroman, or anagrelide. The primary outcomes were hematocrit control and complete hematologic response (CHR).

In the cohort, the median age was 66.4 years and 72.8% of patients were male. There were 41.6% of patients were treated with ruxolitinib, 34% were hydroxyurea resistant, and 60% were hydroxyurea intolerant.

Higher rates of hematocrit control were observed in the ruxolitinib group compared with the BAT group (RR, 1.907; 95% CI, 1.135-3.205; P =.015). Ruxolitinib was also associated CHR compared with BAT (RR, 1.965; 95% CI, 1.025-3.768; P =.042).

Among patients with hydroxyurea-resistant or intolerant PV, higher rates of CHR (RR, 2.28; 95% CI, 1.36-3.84; P <.01), at least a 50% reduction in the MPN-SAF score (RR, 3.19; 95% CI, 1.21-8.46; P =.02), and PGIC score (RR, 6.86; 95% CI, 3.45-13.63; P <.01).

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Neutrophil-to-lymphocyte ratio as a prognostic indicator of mortality in Polycythemia Vera: insights from a prospective cohort analysis

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Tiziano Barbui, Alessandra Carobbio, Arianna Ghirardi, Francesca Fenili, Maria Chiara Finazzi, Marta Castelli, Alessandro M. Vannucchi, Paola Guglielmelli, Alessandro Rambaldi, Naseema Gangat & Ayalew Tefferi

Abstract

We analyzed the neutrophil-to-lymphocyte ratio (NLR) in 1508 patients with PV and found that those with an NLR ≥ 5 were generally older, had a longer disease history, and had higher cardiovascular risk factors, more arterial thrombosis, and more aggressive blood counts, indicating a more proliferative disease. NLR was an accurate predictor of mortality, with patients with NLR ≥ 5 having significantly worse overall survival and more than twice the mortality rate compared to those with NLR < 5. Multivariable models confirmed that increasing age, previous venous thrombosis and NLR ≥ 5 were strong predictors of death, further influenced by cardiovascular risk factors. We examined the interaction between NLR and the number of cardiovascular risk factors and found a progressive trend of increased mortality risk for NLR values ≥ 5 in addition to the presence of more than one risk factor. In conclusion, patients with NLR ≥ 5 require careful monitoring and management of cardiovascular risk factors because they increase mortality when associated with progressive levels of NLR.

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In the Trenches: Dr. Anthony Hunter

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1. Why did you choose hematology as a specialty, specifically MPNs?

There was no singular moment that I knew this would be my career path. I have always been fascinated by the biology and genetics of blood cancers. As I was exposed to clinical care throughout my medical training, I continually found myself drawn to patients with hematologic malignancies. I find MPNs in particular to be such unique diseases, and have observed the significant unmet clinical need within the field. Most importantly, I greatly enjoy the ability to develop a long-term relationship with my MPN patients and to hopefully have a positive impact on their lives.

2. Can you share your approach to MPN patient care?

If I can summarize this in four words, I would describe my approach as 1) informative, 2) patient-centered, 3) individualized, and 4) proactive. I find that many patients who arrive at my clinic do not have a sufficient understanding of their disease, even those who have been dealing with their disease for many years. With all of my patients, I try to educate and provide a thorough understanding of their disease. Particularly at initial consultations, I spend a great detail of time discussing their disease, including the biology of MPNs, how we diagnose them, the potential complications, as well as the available potential treatment options. I find that providing this thorough overview helps patients to feel empowered and more in control of their disease, and provides a good framework for further discussions moving forward. As we develop diagnostic, treatment, and monitoring plans, I feel strongly that there is no “one-size-fits-all” approach. Every patient is unique, and I try to discuss all reasonable paths forward with my patients taking into account their health, personal goals, and concerns, as well as their unique disease characteristics. I feel that shared decision-making is vital to determining a treatment plan that works for all involved parties. Lastly, the clinical care of MPNs has historically taken a more passive approach. I feel that a proactive approach is more appropriate given our current understanding of MPNs and the available treatments, and seek to employ this in my practice. Despite many advances in the past decade, we have a long way to go in improving and extending the lives of patients with MPNs. I remain actively involved in cutting-edge MPN research, integrating this into the clinical care of my patients as appropriate.

3. What advice would you impart to MPN patients?

I’m going to cheat here and give two because I think that they are both important. The first is that “knowledge is power”; cliché, I know! However, it is vital to learn about your disease and understand the potential complications that could arise, what treatments are available to you, and what you should be watching out for. Along those same lines, it is important to recognize that you will always be your own strongest advocate. It’s critical to actively participate in your care journey and speak up if you have concerns. There are many great physicians out there, but we are human; it is important to express your fears and concerns and to seek out the care team that best fits you.

Jakafi, Pegasys Combination Beneficial in Newly Diagnosed Polycythemia Vera

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November 4, 2024

Author(s): Alex Biese

Fact checked by: Spencer Feldman

Among patients with who were newly diagnosed polycythemia vera (PV), treatment with Jakafi (ruxolitinib) and low-dose Pegasys (pegylated interferon alfa-2a) was found to be beneficial, resulting in high rates of hematologic and molecular response, research has shown.

Findings from the two-year end-of-study results of the phase 2 COMBI II clinical trial, published in Blood Advances, showed that the combination treatment was associated with improvements to patients’ cell counts with what researchers described as acceptable toxicity.

Researchers utilized the participation of 25 patients with PV, with a median age of 70 years. According to the study, 14 patients (56% of participants) achieved remission at 24 months, with three (12%) attaining complete remission and 11 (44%) reaching partial remission. Researchers reported what they observed as significant reductions to abdominal discomfort, night sweats, itching and bone pain, while the median JAK2V617F VAF was decreased from 47% to 7% and 60% of patients achieved molecular remission.

One of the 25 patients dropped out of the study within two years, while one patient discontinued both drugs while two patients each discontinued Jakafi and Pegasys and continued stand-alone therapy with the other drug.

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Age, Race, Insurance Status Can Predict CV Mortality for Those With MPNs

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November 2, 2024

Author(s): Mary Caffrey

Among those diagnosed with myeloproliferative neoplasms (MPNs), age, race, marital status, and insurance status can help predict cardiovascular mortality (CVM), based on an analysis of more than 24,000 US patient records.1

A new study finds that clinical factors and social determinants of health can predict cardiovascular mortality among patients with myeloproliferative neoplasms.

| Image Credit: yodiyim – stock.adobe.com

The study, appearing this week in Therapeutic Advances in Hematology,1 aimed to identify prognostic factors that can guide clinicians in treating patients with MPNs, which are a group of hematopoietic stem cell disorders that are generally diagnosed in individuals after age 40; according to the Leukemia & Lymphoma Society, most patients are diagnosed in their 60s or 70s.

The team from Sun Yat-sen University in China culled records for more than 48,000 patients diagnosed with MPNs between 2000 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database, but narrowed their analysis to those records for patients that lived at least a year and included other essential clinical information. That left a database of 24,277 patient records.

Among the demographic findings:

  • The database included 10,409 patients (42.9%) with polycythemia vera (PV), 3229 (13.3%) with myelofibrosis (MF) and 10,639 (43.8%) with essential thrombocythemia (ET).
  • Prevalence of the condition was higher among White males in PV and MF compared with females in ET.
  • At diagnosis, only 8.0% were younger than 40 years old; 29.0% were 40-59 years old, 47.0% were 60-79 years old; and 16% were older than 80 years of age.

The analysis took a snapshot of patients at 200 months of follow-up (16 years, 8 months) and found that the cumulative mortality was the following CVD (17.9%), other noncancer (22.1%), MPN (18.8%), and other cancers (6.1%). However, investigators found that more than 50% of patients initially diagnosed with MF died from their primary disease during this period, which may be due to conversion of their disease to acute myeloid leukemia.

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Ruxolitinib Plus Pegylated Interferon Alfa-2a Show Promise in Newly Diagnosed Polycythemia Vera

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November 1, 2024

Author(s): Alexandra Gerlach, Associate Editor

Ruxolitinib (Jakafi; Incyte Corp) in combination with pegylated interferon alfa-2a demonstrated efficacy and tolerability in patients with newly diagnosed polycythemia vera (PV). According to the 2-year end-of-study results from the phase 2 COMBI 2 clinical trial (EudraCT2018-004150-13), the treatment improved cell counts, bone marrow cellularity, and fibrosis in patients with PV.1

In the phase 2 COMBI 2 trial, researchers evaluated the safety and efficacy of ruxolitinib and low-dose peg-IFN-α2a in patients with newly diagnosed PV.

Image Credit: © MdBabul – stock.adobe.com

PV is a chronic, progressive myeloproliferative neoplasm characterized by the overproduction of red blood cells. The excess cells thicken the blood, slowing its flow and contributing to serious complications, such as blood clots. Almost all patients with PV have the JAK2V617F mutations, and the JAK2V617F variant allele frequency (VAF) is key for determining outcomes, including thrombosis and progression to myelofibrosis.2-4

Ruxolitinib is a Janus kinase inhibitor approved by the FDA in 2011 and is indicated for the treatment of patients with high-risk MF with reduced abnormal expression of PF4, which can lead to decreased fibrosis. It is additionally indicated as a second-line treatment of PV for patients who have an inadequate response to or cannot tolerate hydroxyurea. In the COMBI 2 trial, researchers assessed the efficacy of ruxolitinib in combination with pegylated interferon alfa-2a (peg-IFN-α2a) (Pegasys ProClick; Genentech), an injection commonly used to treat hepatitis B and C infections. According to data from prior studies, peg-IFN-α2a has been shown to induce durable hematologic and molecular remissions in patients with PV. However, approximately 20% to 40% of patients are intolerant or show limited response to peg-IFN-α2a.5-8

In the phase 2 COMBI 2 trial, researchers evaluated the safety and efficacy of ruxolitinib and low-dose peg-IFN-α2a in patients with newly diagnosed PV in an effort to counterbalance intolerance to peg-IFN-α2a. The primary end point was safety, with secondary end points including efficacy, based on hematologic parameters, quality-of-life measurements, and JAK2V617F variant allele frequency (VAF).8

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FORUS Therapeutics Inc. and PharmaEssentia Corporation Have Entered Into an Exclusive Licensing Agreement for The Registration and Distribution of BESREMi(R) (ropeginterferon alfa-2b) for The Treatment of polycythemia vera (PV), in Canada

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October 31, 2024 8:30 AM EDT | Source: FORUS Therapeutics Inc.

  • Under the terms of the agreement, FORUS is licensing BESREMi from PharmaEssentia for PV in Canada, with potential expansion to other investigational myeloproliferative neoplasms (MPN) indications.
  • FORUS will oversee the drug registration and commercialization of BESREMi in Canada, including securing approval of BESREMi in PV and meeting certain milestones.

Oakville, Ontario–(Newsfile Corp. – October 31, 2024) – FORUS Therapeutics Inc (“FORUS”) and PharmaEssentia Corporation (“PharmaEssentia”) have entered into an exclusive licensing agreement for the registration and distribution of BESREMi® (ropeginterferon alfa-2b) for the treatment of polycythemia vera (PV), in Canada.

“On behalf of the FORUS Therapeutics team, I am truly excited to announce this licensing agreement with PharmaEssentia and to commence the process of commercializing BESREMi in Canada. BESREMi represents the second novel therapeutic in the FORUS hematology-oncology pipeline and is another important step in fulfilling the organization’s mission and vision. We are committed to rapidly advancing BESREMi through the regulatory and reimbursement pathways to ensure that PV patients in Canada have broad access to this novel medication,” said Kevin Leshuk, President and CEO of FORUS. “We are making this announcement today to support the momentum created by the September 12th, Annual MPN Awareness Day and the International Congress on Myeloproliferative Neoplasms, recently held in Brooklyn, New York. We believe that continuing to elevate awareness with the goal of meeting the unmet needs of the MPN community is critical to making a difference in the lives of patients.”

“BESREMi is an important and significant development for clinicians who treat patients with PV. BESREMi as a potential future treatment option is particularly critical for Canada, where treatment options are notably limited for these patients,” says Dr. Shireen Sirhan, a founding member and the current President of the Canadian MPN group, and Vice-President for research in MPNs of the Groupe Québécois de recherche en LMC-NMP. “Canadian physicians have played a significant role in the clinical development program for BESREMi and we look forward to having this important treatment available in the clinic for our patients in need.”

“This is very exciting news for the PV community across Canada,” says Doug Chisholm and Patricia Saluk, the former and current Chair, Board of Directors of the Canadian MPN Network Patient Advocacy group. “Polycythemia vera is a rare blood cancer and the future commercialization of BESREMi in Canada offers highly anticipated new hope for patients, families, and their support networks. We hope the Canadian regulatory and payor systems will work as quickly as possible to ensure our patient community has access to this much needed new treatment regimen.”

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Inrebic May Reduce Spleen Volume in Myelofibrosis

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October 31, 2024

Author(s): Alex Biese

Fact checked by: Spencer Feldman

Among patients with myelofibrosis who have been previously treated with Jakafi (ruxolitinib), treatment with Inrebic (fedratinib) was beneficial, particularly regarding spleen volume reduction (SVR) when compared to treatment with otherwise best-available therapy (BAT), researchers have found.

Findings from the phase 3 FREEDOM2 trial were published in The Lancet Hematology.

“In the FREEDOM2 trial, patients with myelofibrosis previously treated with [Jakafi] showed superior SVR and symptom response when treated with [Inrebic] compared with BAT (predominantly [Jakafi]),” researchers concluded in the study. “The safety profile of [Inrebic] was consistent with previous trials, and mitigation measures effectively managed known adverse events. Overall, the results indicate that [Inrebic] is a promising option for second-line JAK inhibitor treatment of myelofibrosis.”

Inrebic, a type of tyrosine kinase inhibitor, works by blocking JAK2 and other proteins — which, as defined by the National Cancer Institute, may help keep abnormal blood cells or cancer cells from growing. It was approved by the Food and Drug Administration for the treatment of patients with myelofibrosis in 2019.

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