Global Myeloproliferative Disorders Drugs Market to Reach $12.9 Billion by 2030

Posted on May 18, 2023May 18, 2023 by mpn_admin

ReportLinker

Wed, May 17, 2023 at 10:51 AM EDT

The global economy is at a critical crossroads with a number of interlocking challenges and crises running in parallel. The uncertainty around how Russia`s war on Ukraine will play out this year and the war`s role in creating global instability means that the trouble on the inflation front is not over yet.

New York, May 17, 2023 (GLOBE NEWSWIRE) — Reportlinker.com announces the release of the report “Global Myeloproliferative Disorders Drugs Industry” – https://www.reportlinker.com/p06032290/?utm_source=GNW
Food and fuel inflation will remain a persistent economic problem. Higher retail inflation will impact consumer confidence and spending. As governments combat inflation by raising interest rates, new job creation will slowdown and impact economic activity and growth. Lower capital expenditure is in the offing as companies go slow on investments, held back by inflation worries and weaker demand. With slower growth and high inflation, developed markets seem primed to enter into a recession. Fears of new COVID outbreaks and China’s already uncertain post-pandemic path poses a real risk of the world experiencing more acute supply chain pain and manufacturing disruptions this year. Volatile financial markets, growing trade tensions, stricter regulatory environment and pressure to mainstream climate change into economic decisions will compound the complexity of challenges faced. Year 2023 is expected to be tough year for most markets, investors and consumers. Nevertheless, there is always opportunity for businesses and their leaders who can chart a path forward with resilience and adaptability.

Global Myeloproliferative Disorders Drugs Market to Reach $12.9 Billion by 2030

In the changed post COVID-19 business landscape, the global market for Myeloproliferative Disorders Drugs estimated at US$9.3 Billion in the year 2022, is projected to reach a revised size of US$12.9 Billion by 2030, growing at aCAGR of 4.2% over the period 2022-2030. Ph+ Chronic myelogenous leukemia (CML), one of the segments analyzed in the report, is projected to record 3.5% CAGR and reach US$9.2 Billion by the end of the analysis period. Taking into account the ongoing post pandemic recovery, growth in the Ph- Myeloproliferative Neoplasms (MPNs) segment is readjusted to a revised 6.1% CAGR for the next 8-year period.

The U.S. Market is Estimated at $2.5 Billion, While China is Forecast to Grow at 7.3% CAGR

The Myeloproliferative Disorders Drugs market in the U.S. is estimated at US$2.5 Billion in the year 2022. China, the world`s second largest economy, is forecast to reach a projected market size of US$2.7 Billion by the year 2030 trailing a CAGR of 7.3% over the analysis period 2022 to 2030. Among the other noteworthy geographic markets are Japan and Canada, each forecast to grow at 1.9% and 3% respectively over the 2022-2030 period. Within Europe, Germany is forecast to grow at approximately 2.8% CAGR.

Individual Patient Factors Drive Treatment Decisions in MPNs

Posted on May 18, 2023May 18, 2023 by mpn_admin

May 4, 2023

Brittany Lovely

Onco-nursing experts highlight the best practices and latest treatment regimens for patients presenting with the 3 most common myeloproliferative neoplasms: myelofibrosis, polycythemia vera, and essential thrombocythemia.

Although literature, guidelines, and laboratory data are available to guide treatment decisions for patients with myeloproliferative neoplasms (MPNs), most decisions in clinical practice stem from individual presentations, according to onco-nursing experts.¹

During a Medical Crossfire^® at the 48th Annual Oncology Nursing Society Congress, specialists highlighted the best practices and latest treatment regimens for patients presenting with the 3 most common MPNs: myelofibrosis, polycythemia vera (PV), and essential thrombocythemia (ET).

The crossfire was chaired by Jill Brennan-Cook, DNP, RN, GERO-BC, an associate professor in the ABSN program and a member of the Healthcare in Adult Populations Division at Duke University School of Nursing.

Brennan-Cook was joined by Abdulraheem Yacoub, MD, an associate professor of medicine and clinical director of ambulatory clinics at the University of Kansas Cancer Center, Ilene Galinsky, BSN, MSN, ANP-C, a research nurse practitioner at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, and Brandi Ligon, MS, BSN, RN, AGPCNP-BC, a hematology and oncology nurse practitioner at AdventHealth.

Myelofibrosis

Clinical, laboratory, and pathologic analyses are needed to make a diagnosis of myelofibrosis, Yacoub explained in an overview of the disease. Updated major criteria include megakaryocytic proliferation and atypia with reticulin and/or collagen fibrosis of grade 2 or 3; presence of a JAK2, CALR, or MPL mutation or other clonal markers such as ASXL1, EZH2, TET2, IDH1/2, among others, or the absence of reactive myelofibrosis; and not meeting other World Health Organization criteria for myeloid malignancies.2 In addition to these 3 criteria, patients must also present with 1 minor criteria which can include the following: anemia not related to a comorbid condition; leukocytosis at least 11 × 109/L; palpable splenomegaly, lactate dehydrogenase increased above the upper limit of normal; and leukoerythroblastosis.²

“Patients with myelofibrosis have unique presentations and each patient has unique therapeutic needs that requires collaboration between the physician, the nurse, the nurse practitioner, that pharmacist the whole health care system to try to provide better care,” Yacoub said. “There is also a significant education need for practitioners, as well as the patients and their caregivers to teach them more about myelofibrosis, how to approach the disease, and [identify] the unmet needs so that we can work as a team to advance the field.”

Despite MPNs entering clinical discussions nearly a century ago, most of the knowledge and treatments have been generated in the past 15 years, Yacoub explained. As overactive JAK signaling presents as a hallmark of myelofibrosis agents targeting the signaling mechanism have come into use. When JAK/STAT signaling increases, myeloproliferation and abnormal levels of cytokines can trigger presentations of myelofibrosis such as abnormal cell counts, bone marrow fibrosis (which prevents normal hematopoiesis), and splenomegaly, a common occurrence in up to 90% of patients with myelofibrosis.³

The best avenue for the management of patients with myelofibrosis can evolve over time, Yacoub said, but noted that 3 goals are common—reduce splenomegaly, improve symptoms, and improve survival. For example, splenomegaly, chronic inflammation, fatigue, among other symptoms have resulted in reductions in quality of life. “This is a unique feature of MPNs which requires extra attention and examination by providers,” Yacoub said. “There have been tools developed to quantify patients’ symptoms and address them appropriately.”

Finally, Yacoub noted that patients are treated based on symptom burden and risk. Based on the National Comprehensive Cancer Network (NCCN) guidelines, low-risk and intermediate-1 patients should undergo observation if asymptomatic, or ruxolitinib (Jakafi) if symptomatic. They may also be treated for cytopenias and select patients may qualify for transplant.

For those who are high-risk or intermediate-2, transplant, ruxolitinib (platelet count >50), fedratinib (Inrebic; platelet count >50), or pacritinib (Vonjo; platelet count <50) should be considered. Anemia and thrombocytopenia should also be managed appropriately. Alternatively, clinical trial enrollment are options for all-risk patients.⁴

Despite guidelines for these treatments, the time to progression in myelofibrosis varies with most experiencing progression in the first 10 years of a diagnosis. Long-term, progressive complications such as cytopenias, constitutional symptoms, organomegaly and extramedullary hematopoiesis have been reported, as well as short-term vascular events.¹

There is also the potential for evolution to leukemia, which Yacoub noted makes the unmet need for patients who progress on JAK inhibitors of importance.

“We are lucky that the research has identified many targets,” Yacoub said, noting that there is a long way to go.

In a case study of a patient with myelofibrosis, Galinsky, noted that a 75-year-old woman presented with progressive disease that was ultimately defined as post-ET myelofibrosis, along with a prognosis of approximately 8 years after using scoring systems who was about to undergo treatment for symptom management.

“It’s important that, in addition to your clinical lab studies, symptoms are subjective and objective and it’s always important to communicate with your patients,” Galinsky said. “How do you treat these patients? You want to think about where they are in their life. [The case study patient] happens to be older, so she is not a transplant candidate, but at [Dana-Farber] up to 75 years are referred for transplant consult just to get her HLA typing. That’s important to do for all patients. What needs to be done in regard to her symptoms? You want to fix their anemia and splenomegaly, and the JAK inhibitor is the way to go—so we started at low-dose ruxolitinib.”

Galinsky noted it is important to rule out other causes of symptoms prior to starting therapy. “Always in these patients, it’s not always what it looks like. Just because a patient has myelofibrosis, you cannot blame everything on myelofibrosis.”

“My take-home message is always, always look at the patient. Always look at their labs, but always talk to the patient—what are they reporting that their symptoms are?” Galinsky added. “If their numbers are changing and they’re not feeling well, always ask if they are taking their drug. If they are not taking their drug—why? If they are having adverse effects [AEs], it’s our job to help them [manage the symptoms].”

PV

“PV is the most common of the 3 MPNs and shares many characteristics with myelofibrosis…but the hallmark of PV is the excessive production of red [blood] cells, white [blood] cells, and platelets,” Yacoub said. Fortunately, Yacoub said, patients have normal life expectancy with PV and therefore management goals focus on achieving cytoreduction, improving symptoms, and avoiding treatment-related toxicities.

Cytoreductive agents are reserved for patients with high-risk disease and for those with uncontrolled disease manifestations with phlebotomy, which is the immediately available tool to reduce blood counts, Yacoub explained. Aspirin is essential for all patients. In a study of therapies used for PV, it was noted that most physicians were using hydroxyurea either with aspirin or phlebotomy. Even though hydroxyurea is the most common and up to 70% of patients respond to therapy, Yacoub said that for the 30% who do not respond or have resistance, alternative options are needed.⁵

“Interferons, which are becoming a standard first-line therapy, are still underused,” Yacoub noted. For example, ropeginterferon-alfa-2b-njft (Besremi) was approved for first- and second-line treatment of patients with PV and has shown far superior long-term outcomes compared with hydroxyurea in the PROUD-PV study (NCT01949805).⁶

“It’s not uncommon for a person to [receive a diagnosis of] PV randomly, just going for blood work and [they] have elevated hemoglobin and hematocrit and sometimes white blood cells and sometimes platelets,” Brennan-Cook said in a case discussion of a patient with PV. “Approximately 30% of patients who are newly diagnosed come in after they’ve had a thrombotic event. So, they find out as they are admitted to the hospital for a [blood] clot that they have PV.”

Brennan-Cook said that any patient with an MPN should be seen by a specialist. “For those of us who work at large academic medical centers that is easy, but a lot of our patients have the travel quite a distance to be seen by an MPN specialist. That confounds a lot of the care that they get and it complicated the treatment because sometimes they have to spend a whole day at the center and they have to drive several hours and that [can] impact adherence.”

Although management of symptoms sounds simple—prevention of thrombotic events being paramount—Brennan-Cook said that maintaining quality of life is also a consideration in nursing interactions. Health literacy has a role in adherence, she noted, and understanding what knowledge patients have at baseline can guide how nurses can best communicate with them regarding treatments. She cited NCCN guidelines as a resource for patients.

Nurses should consider symptom burden, especially fatigue, which is present in approximately 80% of patients with PV. Brennan-Cook said that this can play a role in whether they make it to not only social events but appointments as well. She recommends yoga and motivational conversations that bring the patient into the treatment decision-making, rather than the nurse providing recommendations without patient buy in.

“The symptoms for PV can change,” Brennan-Cook said, highlighting that symptoms such as pruritus may evolve over time and necessitate concurrent treatments. Tobacco use has also been associated with the increased symptom burden.

Finally, Brennan-Cook noted that patients with PV can appear healthy, but the unknown of their disease afflicts them like other oncologic diagnoses. “They know it’s progressive, they don’t know if [their PV] is going to progress to myelofibrosis because approximately 20% progress to myelofibrosis and a small amount to acute myeloid leukemia, but they don’t know when or if it is going to happen,” she said. “So, every month when they are going for their labs that thought is with them. Whatever you can do to work with them, thinking about quality of life, thinking about activity levels, and staying healthy on their own, it’s important to have those conversations.”

ET

The lowest-risk MPN, ET manifests as isolated thrombocytosis, with a high risk of thrombosis and bleeding. Half of patients present with a JAK2 mutation, thrombocytosis, and megakaryocyte proliferation. Additionally, the disease has a high symptom burden.⁷

“ET is a bunch of megakaryocytes and platelets that take over the bone marrow,” Ligon said in a presentation on clinical observations with ET. Symptoms can present as headaches, dizziness, fainting, and vision changes, which are the most common. Patients may also experience chest pain, numbness, burning sensation in the hands, and bleeding events.

Patients are divided into risk categories based on age, mutational status, and thrombosis history.4 Despite the division based on cardiovascular risk, Yacoub explained that patients should be treated if they are symptomatic regardless of risk status. “For patients who are not high-risk, we treat them based on symptoms,” he said. “This can include cytoreductive agents or observation only or any of the other options that we have.”

Hydroxyurea is a mainstay in treatment for this population, and ruxolitinib is also used in certain cases, but Yacoub added that ropeginterferon alfa-2b is under investigation in the phase 3 SURPASS ET trial (NCT04285086). “Hopefully if these studies are successful the same drug that is used in PV will be approved and an option for patients with ET.” Another agent is bomedemstat, which is an LSD1 inhibitor that targets megakaryocytes, which has demonstrated normalization of platelet counts.⁸

“What is our role as oncology nurses? The biggest thing is symptom management for these patients, reductions of complications, reducing the risk of thrombus,” Ligon said. “[We also must] make sure that these patients know that when they take hydroxyurea that they are wearing gloves when they administer the medication because they can cause toxicities through the skin.”

Ligon noted that there is an MPN symptom management app available for patients.⁹

What’s Next?

As for the future of MPNs, the panel noted that as more medicines are introduced and diagnoses are made earlier through educational efforts, a new wave of treatment may emerge.

“We’re making major progress at all aspects of MPNs,” Yacoub said. “We’re a lot better at making a diagnosis now, we have better tools, we are doing whole genome sequencing or next-generation sequencing, so we are learning a lot more about disease biology and are describing it better. We have a much more informed discussion with patients about their futures now.”

“Being able to target some of these mutations with the drugs that are coming down the pipeline, would allow these patients to have more control and have more personalized medicine when it comes to treating these diagnoses,” Ligon said. “I also like that some of our community physicians can be an asset to the physicians at the bigger centers. A lot of times, they can work in conjunction together so that patients do not have to travel as far, maybe only every 3 months, or so.”

“Communication and collaboration make a big difference,” Brennan-Cook concluded.

References

Brennan-Cook J, Galinsky I, Ligon B, Yacoub A. Medical Crossfire®: exchange between onco-nursing experts on MPN treatment and symptom management along the care continuum. Presented at: 48th Annual Oncology Nursing Society Congress; April 26, 2023; San Antonio, TX.
Arber DA, et al. Kvasnicka HM, Orazi A, et al. The international consensus classification of myeloid neoplasms and acute leukemias: myeloproliferative neoplasms. Am J Hematol. 2023;98(3):544-545. doi:10.1002/ajh.26821
Spivak JL. Myeloproliferative neoplasms. N Engl J Med. 2017;376(22):2168-2181. doi:10.1056/NEJMra1406186
NCCN. Clinical Practice Guidelines in Oncology. Myeloproliferative neoplasms, version 3.2022. Accessed April 26, 2023. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf
Grunwalk MR, Kuter DJ, Altomare I, et al. Treatment patterns and blood counts in patients with polycythemia vera treated with hydroxyurea in the United States: an analysis from the REVEAL study. Clin Lymphoma Myeloma Leuk. 2020;20(4):219-225. doi:10.1016/j.clml.2019.09.601
Kiladjian JJ, Klade C, Georgiev P, et al; PROUD-PV Study Group. Long-term outcomes of polycythemia vera patients treated with ropeginterferon alfa-2b. Leukemia. 2022;36(5):1408-1411. doi:10.1038/s41375-022-01528-x
Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. doi:10.1182/blood-2016-03-643544
Gill H, Palandri F, Ross DM, et al. A phase 2 study of the LSD1 inhibitor bomedemstat (IMG-7289) for the treatment of essential thrombocythemia (ET). Blood. 2022;140(suppl 1):1784-1787. doi:10.1182/blood-2022-159047
The MPN Genie. Canadian Research Foundation. Accessed April 26, 2023. https://www.cmpnrf.ca/genieapp

Combination of azacitidine, venetoclax and ruxolitinib in blast phase myeloproliferative neoplasms.

Posted on May 18, 2023May 18, 2023 by mpn_admin

Thomas Systchenko, Jean-Claude Chomel, Pilar Gallego-Hernanz, Niels Moya, Déborah Desmier, Natacha Maillard, Arthur Bobin, Mathilde Vonfeld, Hélène Gardeney, Emilie Cayssials E, José Torregrosa

First published: 14 May 2023

Summary

Myeloproliferative neoplasms in blastic phase (MPN-BP) have a dreadful prognosis. We report the characteristics and outcomes of five MPN-BP patients treated with a never-before-described combination of azacytidine and venetoclax (to control BP transformation), added to ruxolitinib (needed to control constitutional symptoms). Median age was 76 years (range 72–84), and worst performance status was 2. The overall response rate was 80%, and the complete remission rate was 40%. With median follow-up of 10.0 months (range 4.2–13.4), median overall survival was 13.4 months (95% CI 4.2–13.4). We did not detect any unexpected treatment-related toxicity, and quality of life was improved.

INTRODUCTION

Philadelphia-negative myeloproliferative neoplasms in blastic phase (MPN-BP) have a dreadful prognosis with median survival of fewer than 6 months. For non-transplant candidates, there is still no standard treatment.¹ The combination of azacitidine (AZA, hypomethylating agents [HMA]) and venetoclax (VEN) has become the new standard of care for de-novo acute myeloid leukaemia (AML),² particularly for non-transplant candidates. To note, post-MPN AML was excluded from the registering trial. The combination of HMA and ruxolitinib (RUX) has been reported to achieve prolonged overall survival (OS) for MPN in accelerated and blast phase in a phase 2 study.³ However, none of these treatments have become the standard of care for MPN-BP. The AZA-VEN combination seems the most attractive therapy for leukaemic transformation, and the addition to RUX appears of interest as a way of keeping the constitutional symptoms and/or splenomegaly of myelofibrosis under control. To the best of our knowledge, no data have evaluated the safety and effectiveness of the combination of AZA, VEN and RUX in this setting. In the present work, we report the characteristics and outcomes of five patients with MPN-BP treated with this combination.

METHODS

Study design and patients

We reported data from five patients with MPN-BP who received AZA, VEN and RUX in our institution. MPN-BP was defined by ≥20% blasts in the peripheral blood or bone marrow, with a documented prior diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or myelofibrosis (MF).⁴ This study was conducted in accordance with ‘good clinical practice’ (GCP) and applicable regulatory requirements, including the 2008 version of the Declaration of Helsinki. This study complies with the reference methodology MR-004 concerning research reusing data already collected. Patients have the right to access, rectify, oppose and delete their data or to limit their processing.

Treatments

RUX was administered at a dose ≥10 mg twice daily to control constitutional symptoms and/or splenomegaly of myelofibrosis. AZA-VEN was added to treatment after the leukaemic transformation: VEN was administered orally at a daily dose of 200–400 mg on days 1 through 14 at 28 based on expected and observed cytopenia; AZA at a dose of 50 or 75 mg/m² (dose changed to manage haematological toxicity), subcutaneously on days 1 through 7 every 28-day cycle. None of the patients were eligible for allogeneic SCT.

Response and safety

We used modified Cheson criteria for response assessment: complete remission (CR) is defined by no peripheral blood blasts, bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; leukocytes ≥4 ×10⁹/L, haemoglobin ≥10 g/L and platelets ≥100 ×10⁹/L; incomplete remission CRi is defined by no peripheral blood blasts with incomplete count recovery; partial remission (PR) is defined as ≥50% decrease in peripheral blood blasts irrespective of blood counts.⁵ As patients were cytopenic at leukaemic transformation, we retained haematological grade ≥ 3 adverse events that appeared only after the initiation of treatment.

Statistical analysis

OS was estimated using the Kaplan–Meier method and compared between groups by the log-rank test. OS was defined as the time from initiation of treatment to death from any cause. Patients alive at the data cut-off date (February 1, 2023) were censored. The main results are given with their 95% confidence interval (95% CI). Statistical analyses were performed using SAS software version 9.4 (SAS Institute Inc.).

RESULTS

Patient characteristics

At the time of leukaemic transformation, the five patients had myelofibrosis: four secondary MF (two post-PV, one post-ET and one JAK2V617F negative postmyelodysplasic/myeloproliferative neoplasm unclassifiable) and one primary myelofibrosis. The median age was 76 years (range 72–84), and the worse performance status was 2. RUX was administered to control constitutional symptoms for four patients and splenomegaly for two patients. Four patients had RUX before leukaemic transformation. For the first patient, RUX was discontinued at AZA-VEN initiation and resumed after two cycles due to disabling constitutional symptoms. For the next three patients, RUX was continued because the combination appeared safe and effective for the first. Patient characteristics are summarized in Table 1.

ECLIPSE PV Trial Begins Ropeginterferon Alfa-2b Dosing in Polycythemia Vera

Posted on May 16, 2023May 16, 2023 by mpn_admin

May 15, 2023

Caroline Seymour

The first patients have been dosed in the phase 3b ECLIPSE PV trial, which is evaluating an accelerated dosing schedule of ropeginterferon alfa-2b-njft for the treatment of patients with polycythemia vera.

The first patients have been dosed in the phase 3b ECLIPSE PV trial (NCT05481151), which is evaluating an accelerated dosing schedule of ropeginterferon alfa-2b-njft (Besremi) using a prefilled syringe for the treatment of patients with polycythemia vera (PV).¹

“This therapy represents an important addition to the treatment arsenal for PV in the U.S., and clinical data support its use across a broad range of patients regardless of their treatment history,” John Mascarenhas, MD, professor of medicine, hematology, and medical oncology at the Icahn School of Medicine at Mount Sinai in New York, stated in a news release. “This new study is addressing an important therapeutic and clinical question regarding whether treatment utilizing accelerated dosing leads to a more rapid hematologic and molecular response, indicating potential disease modifying activity and long-term disease control.”

In November 2021, the FDA approved ropeginterferon alfa-2b for the treatment of patients with PV.² The agent is a novel monopegylated, long-acting interferon that can be administered once every 2 weeks, or every 4 weeks with hematological stability, for at least 1 year. The agent has the potential to produce durable activity through its pegylation technology.¹

The phase 3b study will evaluate an accelerated dosing schedule for ropeginterferon alfa-2b compared with the current labeled dosing.³ The primary end point of the study is the proportion of patients achieving a complete hematologic response at 24 weeks of treatment, defined as hematocrit below 45% for at least 3 months since last phlebotomy, platelets not exceeding 400 x 10⁹/L, and leukocytes of 10 x 10⁹/L or below.

The study, which will enroll approximately 100 patients with PV in the United States and Canada, will randomly assign patients to receive either the accelerated dosing or the current labeled dosing of 50 µg or 100 µg with 50 mcg titration every 2 weeks. Patients assigned to the accelerated dosing arm will receive a starting dose of 250 µg, then 350 µg at week 2, with a target optimal dose of 500 µg at week 4. Subsequent dosing will remain fixed at the highest tolerated dose for the rest of treatment.

The study will run for 48 weeks and will be followed by a 28-day period of safety follow-up. Patients who respond to treatment will be eligible to participate in a long-term extension phase of the study.

Topline data from the trial are expected by 2024.

“Our goal with this study is to deliver evidence on the potentially enhanced benefits of treating patients with ropeginterferon alfa-2b through this accelerated dosing schedule and to bring additional confidence to clinicians and patients in the utility of the treatment to manage this chronic cancer,” Raymond Urbanski, MD, PhD, U.S. head of Clinical Development and Medical Affairs, said in a news release. “We believe this study will deliver further insight into the potential of ropeginterferon alfa-2b to meet the needs of PV patients.”

References

PharmaEssentia initiates phase 3b trial of ropeginterferon alfa-2b-njft investigatng new dosing regimen for patients with polycythemia vera (PV). News release. May 3, 2023. Accessed May 15, 2023. https://us.pharmaessentia.com/wp-content/uploads/2023/05/ECLIPSE-PV_Initiation_Press_Release_May-3-2023-1.pdf
US FDA approves BESREMI (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed May 15, 2023. https://us.pharmaessentia.com/wp-content/uploads/2021/11/BESREMi-FDA-Approval-November-12-2021.pdf
A study to assess efficacy, safety, and tolerability of P1101 in adult patients with PV. ClinicalTrials.gov. Updated March 27, 2023. Accessed May 15, 2023. https://clinicaltrials.gov/ct2/show/NCT05481151

Mesa Highlights JAK Inhibition for the Treatment of Myelofibrosis

Posted on May 16, 2023May 16, 2023 by mpn_admin

May 15, 2023

Jordyn Sava

In an interview, Ruben Mesa, MD, discussed the currently available JAK inhibitors for patients with myelofibrosis, and what is in store for the field.

JAK inhibitors have paved the way and improved clinical outcomes for patients with myeloproliferative neoplasms over the past decade. Not only have these agents shown significant improvements in efficacy outcomes, but they have demonstrated favorable safety profiles in this patient population.

Currently, 3 JAK inhibitors are approved for patients with myelofibrosis. The first was ruxolitinib (Jakafi), which was approved by the FDA in 2015 and continues to be the main therapy for patients with myelofibrosis. Patients treated with ruxolitinib have had improved splenomegaly and constitutional symptoms, as well as an observed survival benefit.

Following the approval of ruxolitinib came 2 more, including the JAK2 inhibitor fedratinib (Inrebic) which was approved in 2019, and pacritinib (Vonjo) in 2022. Studies of fedratinib have confirmed that the agent is a beneficial second-line treatment option for patients who are ruxolitinib-resistant. Pacritinib also continues to serve as a good treatment option for patients with myelofibrosis and severe thrombocytopenia.

Now, another JAK1/2 inhibitor is in clinical development, known as momelotinib, and is being evaluated in the phase 3 MOMENTUM trial (NCT04173494) for patients who are symptomatic and anemic with advanced myelofibrosis. Those enrolled in MOMENTUM must have previously been treated with a JAK inhibitor, and findings from the study already have revealed clinically significant improvements with momelotinib vs danazol in this patient population.

Data from the MOMENTUM study revealed that 25% of patients treated with momelotinib (n = 130) had a 50%, or more, reduction in patient’s Myelofibrosis Symptom Assessment Form Total Symptom Score (TSS) vs 9% of patients treated with danazol (n = 65), making a proportion difference of 16%. Researchers confirmed this difference to be statistically significant (95% CI, 6–26; P =.0095).

Now, the United States has assigned a Prescription Drug User Fee Act (PDUFA) action date of June 16, 2023.

“We are in an unprecedented period of excitement around new therapies for myeloproliferative neoplasms. Each response and benefit with JAK inhibitors showed a lot of great updated data, [including] momelotinib, which may be approved in 2023,” Ruben Mesa, MD, told Targeted Oncology^TM, in an interview.

In the interview, Mesa, director of the UT Health San Antonio MD Anderson Cancer Center, discussed the currently available JAK inhibitors for patients with myelofibrosis, and what is in store for the field.

Targeted Oncology: Can you discuss some of the approved JAK inhibitors in the myelofibrosis space?

Mesa: For myelofibrosis, we are excited to have 3 FDA-approved therapies, ruxolitinib, pacritinib, and fedratinib, that are all inhibitors of JAK2. Ruxolitinib is from 2011, fedratinib is from 2019, and pacritinib which [was approved in 2022]. Ruxolitinib and fedratinib are both approved in the frontline setting as well as fedratinib in the second-line setting. Now pacritinib is approved in the front and second-line settings for patients who have a platelet count of less than 50,000, and certainly, is a consideration for platelet counts under 100,000 or as a third-line in any patient. These have been a great help.

We have momelotinib coming up on the heels. That might become an approved therapy in 2023. We anticipate all these agents will hopefully improve spleen and symptoms. I think in responding patients, probably all will have a beneficial impact in terms of survival, and we’re excited to have these to build from in this space.

Can you explain the purpose behind the MANIFEST trial and the SIMPLIFY-1 study?

What the MANIFEST study was looking at was pelabresib [CPI-0610] in combination with ruxolitinib, either in the frontline or second-line setting. That was the goal, and we’ve been excited by the data that shows a good depth of response as a single agent with JAK inhibition, as well as potentially extending further the types of benefits that might be seen. That’s helped us to set up the MANIFEST-2 that is ongoing.

The MOMENTUM study, a different study, is [looking at] second-line therapy, symptomatic myelofibrosis with anemia, and showed that momelotinib is clearly superior compared with danazol. These data provide further study updates showing the durability of response screaming symptoms anemia. We are excited about this data.

What is the most new, exciting, and practice changing data in the myeloproliferative neoplasm space?

We are in an unprecedented period of excitement around new therapies for myeloproliferative neoplasms. Each response and benefit with JAK inhibitors showed a lot of great updated data, [including] momelotinib, which may be approved in 2023, as well as pacritinib and validating data with fedratinib. Combinations and phase 2 studies, whether with parsaclisib, venetoclax [Venclexta], pelabresib, or other combinations that may be coming, these combination therapies are truly the way of the future, so it is an exciting time.

AOP Health congratulates FROM on its great scientific work in the field of myeloproliferative neoplasms

Posted on May 16, 2023May 16, 2023 by mpn_admin

May 15, 2023 11:06 AM Eastern Daylight Time

VIENNA–(BUSINESS WIRE)–Fondazione per la Ricerca dell’Ospedale di Bergamo (FROM) announced the publication of the latest results from the LOW-PV trial in the NEJM Evidence.

The findings support a paradigm shift in the treatment of patients with Polycythaemia Vera, a rare kind of blood cancer. AOP Orphan Pharmaceuticals GmbH (AOP Health) congratulates Prof. Tiziano Barbui and his team on this success and is pleased to have contributed to FROM’s important work as a reliable research partner.

Find out more about the trial and its results here.

About AOP Health

The AOP Health Group incorporates several companies including AOP Orphan Pharmaceuticals GmbH with its seat in Vienna, Austria (“AOP Health”). The AOP Health Group is the European pioneer for integrated therapies for rare diseases and in critical care. Over the past 25 years, the Group has become an established provider of integrated therapy solutions operating from its headquarters in Vienna, its subsidiaries and representative offices throughout Europe and the Middle East, as well as through partners worldwide. The claim “Needs. Science. Trust.” sums up the foundation of the Group’s success: establishing trust through a continually high level of investment in research and development and a highly consistent and pragmatic orientation towards the needs of all stakeholders – especially the patients and their families as well as the healthcare professionals treating them.

A Patient Story: Don’t Make It More Difficult

Posted on May 15, 2023May 15, 2023 by mpn_admin

It has been said almost every family has been touched by cancer. I developed AML/APL Leukemia in 2006 and suffered a horrible reaction to chemo that kept me hospitalized for almost 5 months. It was a terribly difficult experience, but I made it through treatment and was so happy to reach the 5-year mark without other major issues. Then, in 2017, a routine physical found elevated platelets and white cells, a
huge red flag. Over the course of a short few months, the platelets rose to over one million. Anxiety followed me, closer than my shadow. Was AML back? Were chemo and hospitalization in my future? After a bone marrow biopsy, I was diagnosed with Essential Thrombocythemia.

For those living with illness, anxiety is simply a reality of life. We constantly scan our bodies for any sign of something wrong. We are nervous about blood test results because…what if…is always on our minds. Something bad happened to us and it made a physical memory we don’t want repeated. If illness has taught me anything, it is the importance of appreciating the present.

We have thousands of thoughts every day and most of them pass as background noise. The mind chatters away and we don’t engage with it too much. But let a scary thought come up, and we get carried away with worry that easily becomes all-consuming. What can be done?

Watch your focus. Treat disturbing thoughts as passing visitors. Let them come and go, and certainly don’t invite them in for tea and conversation. Instead, be present. Breathe deeply, relax your shoulders, and do something tactile. Gently change your focus to the here and now. Don’t chase upsetting thoughts, don’t play with them, chew on them, or try to block them out. Let them pass like clouds in the sky. There is no need to respond. You don’t have to react.

Experience has taught you life is short and can change in a moment. Absolutely everything is temporary. So, why are you wasting your precious time lost in thought, washed in worry? It really doesn’t help anything. You only have one precious life. Live it. Don’t wait. Do whatever you find interesting and rewarding. Your life will only have a deeper meaning when you do things that are meaningful to you.
Quit just getting by. You are so much more than your illness. Take charge. Don’t just survive – thrive.

Bob P.

Kishtagari Discusses Risk Assessment and Treatment Options in Myelofibrosis

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 12, 2023

Targeted Oncology Staff

CASE

A 68-year-old man presented to his physician with symptoms of fatigue, drenching night sweats, abdominal pain, and intermittent fevers lasting 4 months. He also reported increased bruising.
Medical history: type 2 diabetes and atrial fibrillation, both controlled with medication
Spleen palpable 10 cm below the left costal margin
CT scan of the abdomen/pelvis showing splenomegaly with spleen length of 30.3 cm
ECOG performance status: 2

Targeted Oncology: What are the recommendations from the National Comprehensive Cancer Network (NCCN) guidelines in high-risk myelofibrosis?

KISHTAGARI: According to the NCCN guidelines, the symptom assessment score, based on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score [MPN-SAF TSS], is an important objective tool, which I always [use] in my practice to assess the symptom burden. Then you risk stratify these patients based on the platelet count. With a platelet count of less than 50,000/μL, we can treat with pacritinib [Vonjo], and the other option is a clinical trial.

Every patient with myelofibrosis needs to have a transplant evaluation. If a patient is a transplant candidate, they need to proceed with allogeneic hematopoietic cell transplant. With a platelet count of at least 50,000/μL, we can consider ruxolitinib [Jakafi] or fedratinib [Inrebic].¹ One thing I want to highlight, which is something the NCCN guidelines have clearly stated, is that if a patient [experiences progression] on ruxolitinib or fedratinib [and] is intolerant to [either], you can consider pacritinib even if the platelet count is 50,000/μL or more.¹ Even though it is only approved for patients with a platelet count of less than 50,000/μL in the front-line setting,² in the second-line setting, you can consider it for patients with a platelet count of 50,000/μL or more.¹

What therapeutic agents are approved by the FDA for the management of myelofibrosis?

Three agents are FDA approved for [managing] myelofibrosis. All 3 are JAK inhibitors, and there are slight differences in the way they work. The JAK2 mutation was discovered in this disease in 2005, and then there was a focus on inhibiting this mutation, and that led to the development of ruxolitinib. This was FDA approved in 2011 for the [management] of intermediate- or high-risk primary or secondary myelofibrosis.³

The recommended starting dosage of ruxolitinib, if the platelet count is more than 200,000/μL, is 20 mg twice a day. For a platelet count in the range of 100,000/μL to 200,000/μL, you initiate at 15 mg twice a day. For a platelet count in the range of 50,000/μL to less than 100,000/μL, it is recommended to initiate at 5 mg twice daily.⁴ This is something I do not recommend at all; 5 mg twice daily has never been shown to control symptom burden. I think these are patients for whom we need to consider [alternative] therapies. You can initiate it, but I have never seen any improvement at such a low dose of ruxolitinib. You need to monitor the complete blood count [every] 2 to 4 weeks until the dose is stabilized and then as clinically indicated.

What we struggle with in the clinic whenever we see these patients is [this]: If there is a drop in the platelet count, we decrease the dose of ruxolitinib. I do not recommend abruptly interrupting ruxolitinib because there is something called ruxolitinib withdrawal syndrome. Whenever you are trying to mitigate the thrombocytopenia, I think you need to reduce dose. That is probably a better strategy than stopping ruxolitinib altogether.

Fedratinib was approved in 2019 for intermediate-2 or high-risk primary or secondary myelofibrosis.⁵ It is approved for use at a dosage of 400 mg once a day for patients with a baseline platelet count of at least 50,000/μL. That platelet count was chosen because the patients with a platelet count of less than 50,000/μL had severe thrombocytopenia, [which] led to hemorrhage in the clinical trial.

That is the reason why only patients with a platelet count of at least 50,000/μL [should] get fedratinib. There are some dose reductions [recommended for patients who take strong CYP3A inhibitors] or who have renal impairment.⁶

Recently, pacritinib was FDA approved in 2022 for intermediate-or high-risk primary or secondary myelofibrosis in patients with a platelet count of less than 50,000/μL at a dosage of 200 mg twice a day,² with or without food.⁷

What symptoms of ruxolitinib withdrawal should physicians watch for?

The most important symptoms [are similar to those observed] when you suddenly stop steroids. Patients develop hypotension, severe rebound symptoms of their myelofibrosis, and a sudden drop in blood counts. All these point toward ruxolitinib withdrawal syndrome.

How do these 3 agents compare with each other?

Pacritinib, ruxolitinib, and fedratinib have slight differences in their mechanisms of action. The main thing I want to highlight is how pacritinib is different from the other 2 medications. Pacritinib does not inhibit JAK1; it only targets JAK2, in contrast with other medications.^8-10 It preferentially affects the JAK2 V617F mutation but does not affect JAK1,10 and JAK1 has been shown to play an important role in megakaryopoiesis.¹¹

One of the main reasons why this medication does not [cause a] drop in blood count is that it spares JAK1. Interestingly, it also inhibits IRAK1,¹⁰ and right now there is lot of clinical interest, [with respect to] myeloid [malignant tumors], to develop IRAK1 inhibitors because IRAK1 plays an important role in cytokine regulation. By inhibiting both JAK2 and IRAK1, pacritinib has a unique mechanism of action where it can control the symptom and help with the platelet count.

What clinical trials have examined the use of pacritinib in the management of cytopenic myelofibrosis?

There were 2 clinical trials: PERSIST-1 [NCT01773187] and PERSIST-2 [NCT02055781]. PERSIST-1 involved a 2:1 randomization to pacritinib at 400 mg once a day vs the best available therapy [BAT], and the classic primary end point was spleen volume reduction [SVR]. PERSIST-2 included patients [receiving either] first-line or second-line therapy, and they only included patients with a platelet count of no more than 100,000/μL. These were all patients with cytopenic myelofibrosis, an aggressive phenotype, and they were randomly assigned [1:1:1] to receive 400 mg once a day, 200 mg twice a day, or the BAT. This study had the classic end points of SVR at week 24 and the symptom assessment score based on the MPN-SAF TSS at week 24.¹²

What were the results of the PERSIST-2 trial?

In this clinical trial, there was a good distribution of patients who had already received ruxolitinib [45% in the control arm]. Additionally, some patients had received watch-and-wait [monitoring; 19%], some had received hydroxyurea [19%], and some had received steroids or other agents. There was a good distribution of both intermediate- and high-risk [disease] based on the Dynamic International Prognostic Scoring System classification [approximately 70% and 30%, respectively]. The majority of patients in the clinical trial had thrombocytopenia, and approximately 40% of patients had a platelet count of less than 50,000/μL. These patients were equally distributed between the twice-daily pacritinib arm and the BAT arm.¹² The SVR had a 35% cutoff at week 24. Pacritinib 200 mg twice a day improved the SVR compared with the BAT [SVR of at least 35% occurred in 18% vs 3% of patients in the twice-daily experimental arm and control arm, respectively].^7,12

Pacritinib also improved the total symptom [score and the individual symptom score]. These are the different measures we use in all clinical trials with myelofibrosis. [These are] based on the MPN-SAF TSS. Pacritinib decreased the symptom burden compared with the BAT arm [Patient Global Impression assessment scores of “much improved” or “very much improved” were observed in 57% vs 28% of the twice-daily experimental arm and control arm, respectively].¹²

The transfusion burden is very important clinically. Pacritinib 200 mg twice a day improved the transfusion burden by week 24 [among transfusion-dependent patients; the percentage of patients that experienced a reduced burden was 22% in the twice-daily experimental arm vs 9% in the control arm]. Pacritinib also [improved] hemoglobin levels and stabilized the transfusion burden if it was not improved.

What were the adverse events observed in this trial?

The most important adverse event I want to highlight is diarrhea, which was observed in 48% of patients in the twice-daily arm, but rarely was this grade 3 or higher [4%]. Whenever a patient experiences diarrhea, in my practice at least, they respond very well with a single dose of loperamide [Imodium]. You can try that, and if the patient has persistent diarrhea despite the medication, then you need to reduce dose. But in the clinical trial, rarely was the dose reduced.^7,12

Additionally, there was a good percentage of patients with thrombocytopenia [34% for all grades; 32% for grade 3 or higher] and anemia [24% for all grades; 22% for grade 3 or higher], but the majority of patients in the clinical trial had thrombocytopenia and anemia to begin with. For example, if a patient had a platelet count of 56,000/μL at the time of enrollment and they dropped to a platelet count of 49,000/μL, we know that is not clinically significant. However, the clinical trial would capture it as grade 3 thrombocytopenia.

Hematological Cancers Market Set to Witness Explosive Growth By 2031

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 12, 2023

The global Hematological Cancers market research report is focuses on an overall consumption patterns, development trends, sales patterns and sales in key countries of the Hematological Cancers market. The report focuses on global Hematological Cancers vendors, marketing department and competition. This report also provides a detailed information on market share, new developments and business analysis, impact of domestic and major players, discusses the opportunities in terms of emerging size, revenue, expectation, changes in industry regulations, product analysis, decisions strategy, product launch in the market, technological innovation, expansion, geographical location in the market. This study shows that there is a dynamic change in the market when it comes to the benefit of local and regional competition for large companies.

It is aggregated on the basis of different dynamic aspects of industry study. The statistical report is compiled by applying primary and secondary research methodologies. Comprehensive Porter’s five analysis and SWOT analysis are also used to examine the strength, weaknesses, threats and opportunities of the market.

Market Segmentation

The global Hematological Cancers market is segmented on the basis of solution, industry, and end user. Based on solution, the Hematological Cancers market is segmented into component, services. On the basis of industry, the Hematological Cancers market is segmented into manufacturing, others. Based on end user, the Hematological Cancers market is segmented into consumer and enterprises. The global Hematological Cancers market report includes a detailed analysis of the segmentation of this industry by Types and Applications.

Dr Mascarenhas on the Background of the MANIFEST-2 Trial in Myelofibrosis

Posted on May 15, 2023May 15, 2023 by mpn_admin

May 11, 2023

John Mascarenhas, MD

John Mascarenhas, MD, professor of medicine, the Icahn School of Medicine, Mount Sinai, director, the Center of Excellence for Blood Cancers and Myeloid Disorders, member, the Tisch Cancer Institute, Mount Sinai, discusses the background of the phase 3 MANIFEST-2 trial (NCT04603495) investigating the combination of pelabresib (CPI-0610) and ruxolitinib (Jakafi) vs ruxolitinib plus placebo in patients with myelofibrosis who have not been previously treated with a JAK inhibitor.

Previously, the phase 1/2 MANIFEST trial (NCT02158858) evaluated pelabresib alone and in combination with ruxolitinib. In patients who previously received ruxolitinib, the combination produced suboptimal responses, including a spleen volume reduction of at least 35% (SVR35) at week 24 in 20% of patients, Mascarenhas begins. However, in JAK inhibitor–naïve patients, the combination produced a SVR35 at week 24 of 68%, showing that significantly more spleen volume reduction can be obtained with the combination than one would expect with single-agent ruxolitinib, Mascarenhas notes. In addition to improved SVR35 at week 24, the combination led to significant symptom burden improvement in patients who were not treated with a prior JAK inhibitor, Mascarenhas explains.

Additional correlative study data suggested that pelabresib plus ruxolitinib elicited changes in the bone marrow that may be indicative of a more pronounced effect on the level of the disease within the marrow. For example, a hallmark of myelofibrosis is the clustering of atypical megakaryocytes in a tight formation in the bone marrow; however, with the combination therapy, the distance between megakaryocytes increased, which also correlated with spleen volume reduction and symptom improvement, Mascarenhas says. Changes within the bone marrow suggest disease modification stemming from treatment with pelabresib plus ruxolitinib, Mascarenhas emphasizes.

The goal of MANIFEST-2 is to determine the true benefit of pelabresib plus ruxolitinib combination therapy over ruxolitinib monotherapy with a randomized, placebo-controlled study. The phase 3 trial is an ongoing in patients with intermediate- and high-risk myelofibrosis who are naïve to a JAK inhibitor. The results of this study are anticipated because they have the potential to shift the treatment paradigm of myelofibrosis, Mascarenhas concludes.