Tag Archives: mpn

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)

Posted on by

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.

Read more

Broad next generation integrated sequencing of myelofibrosis identifies disease-specific and age-related genomic alterations

Posted on by
Malathi Kandarpa; Dan Robinson; Yi-Mi Wu; Tingting Qin; Kristen Pettit; Qing Li; Gary Luker; Maureen Sartor; Arul Chinnaiyan; Moshe Talpaz
Purpose: Myeloproliferative neoplasms (MPNs) are characterized by the overproduction of differentiated myeloid cells. Mutations in JAK2, CALR and MPL are considered drivers of Bcr-Abl-ve MPNs, including essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic primary myelofibrosis (prePMF) and overt myelofibrosis (MF). However, how these driver mutations lead to phenotypically distinct and/or overlapping diseases is unclear. Experimental Design: To compare the genetic landscape of MF to ET/PV/PrePMF, we sequenced 1711 genes for mutations along with whole transcriptome RNA-seq of 137 MPN patients. Results: In addition to driver mutations, 234 and 74 genes were found to be mutated in overt MF (N=106) and ET/PV/PrePMF (N=31), respectively. Overt MF had more mutations compared to ET/PV/prePMF (5 vs 4 per subject, P=0.006). Genes frequently mutated in MF included high-risk genes (ASXL1, SRSF2, EZH2, IDH1/2 and U2AF1), and Ras pathway genes. Mutations in NRAS, KRAS, SRSF2, EZH2, IDH2 and NF1, were exclusive to MF. Advancing age, higher DIPSS and poor overall survival (OS) correlated with increased variants in MF. Ras mutations were associated with higher leukocytes and platelets, and poor OS. The comparison of gene expression showed upregulation of proliferation and inflammatory pathways in MF. Notably, ADGRL4, DNASE1L3, PLEKHGB4, HSPG2, MAMDC2 and DPYSL3 were differentially expressed in hematopoietic stem and differentiated cells. Conclusions: Our results illustrate that evolution of MF from ET/PV/PrePMF likely advances with age, accumulation of mutations, and activation of proliferative pathways. The genes and pathways identified by integrated genomics approach provide insight into disease transformation and progression, and potential targets for therapeutic intervention.

Read more

The NUTRIENT Trial (NUTRitional Intervention among myEloproliferative Neoplasms): Results from a Randomized Phase I Pilot Study for Feasibility and Adherence

Posted on by

Laura F. Mendez Luque1,2, Julio Avelar-Barragan3, Hellen Nguyen1, Jenny Nguyen1, Eli M. Soyfer1, Jiarui Liu1, Jane H. Chen1, Nitya Mehrotra1, Xin (Helen) Huang1, Heidi E. Kosiorek4, Amylou Dueck4, Alexander Himstead1, Elena Heide1, Melinda Lem1, Kenza El Alaoui1, Eduard Mas1, Robyn M. Scherber5, Ruben A. Mesa6, Katrine L. Whiteson3, Andrew Odegaard1, Angela G. Fleischman1

ABSTRACT

Purpose: Chronic inflammation is integral to Myeloproliferative Neoplasm (MPN) pathogenesis. JAK inhibitors reduce cytokine levels, but not without significant side effects. Nutrition is a low- risk approach to reduce inflammation and ameliorate symptoms in MPN. We performed a randomized, parallel-arm study to determine the feasibility of an education-focused Mediterranean diet intervention among MPN patients.

Read more

Addition of Parsaclisib to Ruxolitinib Decreases Spleen Volume and Improves Symptom Scores Among Patients With Myelofibrosis

Posted on by

Jordan Kadish

02/23/2024

The addition of parsaclisib to stable-dose ruxolitinib treatment decreased spleen volume, improved symptom scores, and yielded acceptable safety among patients with primary or secondary myelofibrosis (MF), according to findings from a phase 2 trial published in Blood Advances.

Abdulraheem Yacoub, MD, The University of Kansas Cancer Center, Kansas City, Kansas, and coauthors explained that although ruxolitinib has demonstrated beneficial results among patients with intermediate- or high-risk myelofibrosis, “suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway.”

In this phase 2 trial, the study authors aimed to measure the potential benefit of adding PI3Kδ inhibitor parsaclisib to ruxolitinib treatment among patients with primary or secondary myelofibrosis who did not have optimal responses to ruxolitinib alone. The primary end points were dosing, efficacy, and safety of this treatment combination.

All patients included in this study stayed on a stable dose of ruxolitinib. Among these patients, 32 were administered parsaclisib at 10 or 20 mg once daily for 8 weeks, then once weekly afterward (daily-to-weekly dosing). Additionally, 42 patients were administered parsaclisib at 5 or 20 mg once daily for 8 weeks, and then 5 mg once daily afterward (all-daily dosing).

Read more

Tixagevimab plus cilgavimab offers COVID-19 protection for haematological cancer patients

Posted on by

Author: Lynda Williams

medwireNews: Tixagevimab and cilgavimab immunoprophylaxis may help protect patients with haematological malignancies from COVID-19 infection and hospitalisation, suggests a research letter published in JAMA Oncology.

The cohort study reports the outcomes of 204 patients who were eligible for immunoprophylaxis with the two fully human SARS-CoV-2-neutralising monoclonal antibodies due to an increased risk of inadequate response to COVID-19 vaccination.

The patients were enrolled between June and September 2022 and followed-up for 6 months, during which time Omicron variants were prevalent in Italy, write Marco Salvini (ASST Sette Laghi, Varese, Italy) and co-authors.

Overall, 130 patients were given a single pre-exposure prophylactic dose of tixageviamb 150 mg and cilgavimab 150 mg, while 74 patients did not receive the treatment.

The majority of patients in the treatment and control arms had lymphoproliferative disorders or multiple myeloma (77 vs 81%), followed by myeloproliferative neoplasms (19 vs 12%) and acute leukaemia (4 vs 7%). Most patients in the two groups were undergoing active treatment (95 vs 92%), with immunotherapy, targeted therapy, chemotherapy, autologous stem cell transplantation or other treatments.

Read more

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

Posted on by

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.

Read more

Clinical Review of Pegylated Interferons Suggests Formulation and Mechanism of Action May Improve Outcomes for MPN Patients

Posted on by
Business Wire
BURLINGTON, Mass., February 21, 2024–(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, oncology and immunology, announced the publication of a manuscript reviewing the clinical safety, efficacy and practical management of treatment with two pegylated interferons – peginterferon alfa-2a and ropeginterferon alfa-2b-njft (marketed as BESREMi®). The manuscript, “Interferons in the Treatment of Myeloproliferative Neoplasms” was co-authored by 12 renowned myeloproliferative neoplasm (MPN) specialists and published in Therapeutic Advances in Hematology. Writing and editorial support were funded by PharmaEssentia, however authors retained full editorial control and provided final approval on all content.
“Interferons are immune modulators that have been used to treat MPNs for more than 35 years. Pegylated interferons are an important therapeutic option and have shown much promise across diseases, including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF),” said Pankit Vachhani, M.D., study author and Associate Professor of Medicine in Hematology/Oncology at University of Alabama at Birmingham. “The manuscript serves as a tool for clinical practice by highlighting the advantages of pegylated interferons, as well as areas where more research is needed to further refine interferon therapies.”

Interferons in the treatment of myeloproliferative neoplasms

Posted on by

Pankit Vachhani, John Mascarenhas , Prithviraj Bose , Gabriela Hobbs, Abdulraheem Yacoub, Jeanne M. Palmer , Aaron T. Gerds, Lucia Masarova, Andrew T. Kuykendall, Raajit K. Rampal, Ruben Mesa and Srdan Verstovsek

Abstract: Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferonbased therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

Read more

Navigating Cytoreduction in MPNs: Benefits, Risks, and Considerations

Posted on by

Jordyn Sava

In an interview with Targeted Oncology, Douglas Tremblay, MD, discussed the significance of cytoreductive therapy in mitigating thrombotic risk in myeloproliferative neoplasms.

According to Douglas Tremblay, MD, cytoreductive therapy has emerged with a pivotal role in mitigating thrombotic risk in the treatment landscape of myeloproliferative neoplasms (MPNs), specifically essential thrombocytopenia (ET) and polycythemia vera (PV).

Despite the evident benefits, each therapy carries unique adverse effects, requiring the careful consideration of patient-specific factors in treatment administration. Deciding when to initiate cytoreductive therapy in patients with chronic MPNs relies on accurate risk assessment, with parameters such as age and prior thrombotic events often guiding treatment decisions.

Frontline therapies, such as hydroxyurea and interferon, manage blood counts for patients with ET and PV, and newer options are emerging, according to Tremblay, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai. However, the long-term implications focus on thrombosis prevention and disease progression.

Ongoing research endeavors aim to delve deeper into surrogate end points and novel therapeutic avenues, promising to further refine and revolutionize the management of MPNs.

In an interview with Targeted OncologyTM, Tremblay discussed the significance of cytoreductive therapy in mitigating thrombotic risk in MPNs, specifically ET and PV.

Read more

Identification of Novel Risk Variants of Inflammatory Factors Related to Myeloproliferative Neoplasm: A Bidirectional Mendelian Randomization Study

Posted on by
Yang Li, Ting Sun, Jia Chen, Lei Zhang

Abstract

Epidemiological and experimental evidence has linked chronic inflammation to the etiology of myeloproliferative neoplasm (MPN). However, it remains unclear whether genetic associations with specific inflammatory biomarkers are causal or due to bias. This study aimed to assess the effect of C-reactive protein (CRP) and systemic inflammatory regulators on MPN within a bidirectional Mendelian randomization design. Genetic associations with MPN were derived from a publicly available genome-wide association study (GWAS) comprising 1,086 cases and 407,155 controls of European ancestry. Additionally, data on inflammation were extracted from two GWASs focusing on CRP and cytokines. The causal relationships between exposure and outcome were explored using the inverse variance weighted (IVW) method. To confirm the final results, multiple sensitivity analyses, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO), were simultaneously employed. Our results suggest that lower levels of macrophage-migration inhibitory factor (IVW estimate odds ratio [OR IVW] per SD genetic cytokines change: 0.641; 95% confidence interval [CI]: 0.427–0.964; p = 0.032) and higher levels of interleukin-2 receptor α (lL2Rα, 1.377, 95% CI: 1.006–1.883; p = 0.046) are associated with an increased risk of MPN. Genetically predicted MPN is related to increased levels of RANTES (IVW estimate β: 0.043, 95% CI: 0.002–0.084; p = 0.039) and interleukin-10 (IVW estimate β: 0.030, 95% CI: 0.001–0.060; p = 0.041). This study provides evidence for a causal relationship between CRP, systemic inflammatory regulators, and MPN, and new insights into the etiology, prevention, and prognosis of MPN.

Read more