Tag Archives: mpn

Ojjaara (momelotinib) approved in Canada for the treatment of myelofibrosis in adults who have moderate to severe anemia

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  • Ojjaara (momelotinib) is the only approved treatment for newly diagnosed and previously treated myelofibrosis patientsi who have moderate to severe anemia and other key manifestations associated with the disease.ii
  • This approval underscores GSK’s commitment to help drive progress for people living with complex blood cancers.

MISSISSAUGA, ON, Nov. 12, 2024 /CNW/ – GSK announced today that Health Canada has approved Ojjaara (momelotinib) for the treatment of splenomegaly and/or disease-related symptoms, in adult patients with intermediate or high-risk primary myelofibrosis (MF), post polycythemia vera MF or post essential thrombocythemia MF who have moderate to severe anemia.iii Ojjaara is the first and only approved medication globally, and now in Canada, that treats both the anemia and other key manifestations of myelofibrosis (newly diagnosed and previously treated).iv

“Treatment options for myelofibrosis-related anemia have been limited. We are proud to offer this treatment alternative for Canadian patients to address this critical unmet need and other myelofibrosis symptoms. With most myelofibrosis patients becoming anemic over time, Ojjaara’s approval represents a significant milestone to improve the outcomes of these patients while also highlighting GSK’s commitment to making an impact in Canada’s hematology oncology space through innovative new treatments,” said Michelle Horn, Interim Country Medical Director, GSK Canada.

Myelofibrosis is a rare blood cancer part of the broader myeloproliferative neoplasms (MPNs) diseases. MPNs have an incidence rate of 2.05 new cases per 100,000 Canadians.v Currently there are between 1,400-2,177 estimated people living with this type of disease in Canada.vi Anemia is a common symptom of myelofibrosis and a major unmet needvii, but awareness among Canadians is low. A 2024 survey shows that 90% of Canadians have heard of anemia but almost 50 per cent do not know about blood cancer related anemia.viii Canadians also have low knowledge of anemia with over 40 per cent of the same respondents saying they know little to nothing about this condition.ix

“Anemia and related transfusions significantly affect the quality of life, prognosis and survival for anemic myelofibrosis patients,” said Cheryl Petruk, CEO of HEAL Canada. “We are excited to witness progress in this rare disease space and to see Ojjaara approved in Canada. This new treatment has the potential to help improve the lives of patients while addressing the disease’s main challenges, namely anemia and other major symptoms.”

Ojjaara is the only once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor.x The approval of Ojjaara by Health Canada is supported by data from the pivotal MOMENTUM Phase III trial, which demonstrated significant improvements in Total Symptom Score (TSS), Transfusion Independence, and Splenic Response Rate.xi Additional support came from a subset of patients in the SIMPLIFY-1 Phase III trial, reinforcing Ojjaara’s efficacy in treating moderate to severe anemia and related symptoms in myelofibrosis patients.xii

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Dr DeAngelo on the Integration of JAK Inhibitors in Myelofibrosis Management

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November 11, 2024

Author(s): Daniel J. DeAngelo, MD, PhD

Daniel DeAngelo, MD, PhD, professor, medicine, Harvard Medical School, chief, Division of Leukemia, institute physician, Dana-Farber Cancer Institute, discusses the integration of JAK inhibitors into clinical practice for patients with myelofibrosis. Lower third needs to be updated

When incorporating JAK inhibitors, such as ruxolitinib (Rituxan), into clinical practice, it is essential to understand both their benefits and the challenges they present, particularly regarding anemia, DeAngelo begins. The phase 3 COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) trials, which initially sought to address symptom control and spleen reduction, demonstrated a notable survival advantage with ruxolitinib over placebo in patients with intermediate-2 or high-risk myelofibrosis, or intermediate-1 disease with symptomatic splenomegaly, he reports. These results led to ruxolitinib becoming the standard of care for high-risk or symptomatic patients, especially as allogeneic transplantation remains limited to select candidates, DeAngelo shares.

A primary consideration with ruxolitinib is its tendency to induce a hemoglobin level drop of approximately 2 points during the first 2 months of treatment due to on-target JAK2 inhibition, which affects erythropoiesis, he continues. Although newer agents are now approved by the FDA specifically for patients with baseline anemia, clinicians using ruxolitinib should anticipate this hemoglobin level decline, he states. Importantly, the initial drop in hemoglobin level does not indicate treatment failure but is a manageable effect that is often misunderstood, leading some oncologists to discontinue or reduce dosing with the drug prematurely, DeAngelo notes.

He goes on to state that his advice for integrating JAK inhibitors into myelofibrosis management plans is to proactively address these expected effects with patients. Patients can be supported through transfusions, growth factors, or alternative JAK inhibitors if needed, according to DeAngelo. In most cases, hemoglobin levels tend to stabilize and improve after the first few months, typically between months 3 and 4, he notes. Setting clear treatment expectations helps ensure patient adherence to therapy and optimizes outcomes when using JAK inhibitors in clinical practice, DeAngelo concludes.

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Frequent Testing for Driver Mutations Critical in Myelofibrosis

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Nov 12, 2024

Researchers from the Munich Leukemia Laboratory in Germany have developed a model that uses 12 genetic markers to accurately stratify patients with myeloproliferative neoplasms (MPNs), according to a study published online ahead of print in Leukemia.

The WHO categorizes classical MPNs—using cytomorphology, bone marrow biopsy, grading of fibrosis, blood counts, and a handful of molecular markers—into four individual entities: chronic myeloid leukemia (CML) and the BCR::ABL1 negative MPNs polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET).

“However, overlaps, borderline findings, or transitions between MPN subtypes occur, and incomplete clinical data often complicates diagnosis,” Manja Meggendorfer, PhD, and the study coauthors wrote.

The researchers analyzed 355 patients with MPN to use the results to stratify MPN entities and provide prognostic information. The investigation revealed the presence of genetically distinct subgroups with different cytogenetic abnormalities, mutations, and JAK2 allele statuses.

“Notably, differences in JAK2 allele status (heterozygous/homozygous) correlated with diverse EFS [event-free survival] and OS [overall survival] outcomes, potentially due to additional prognostic mutations,” the researchers reported. “In contrast, groups with cytogenetic aberrations and additional mutations generally had shorter EFS and poorer OS regardless of the diagnosed entity, aligning with studies on the impact of karyotype and mutation count on survival.”

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JAK2 Mutations Rarely Found in Patients With MPN Living in High Altitude Areas Who Have Unprovoked Thrombotic Events

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Ryner Lai

JAK2 mutations are rarely found in patients with a myeloproliferative neoplasm (MPN) who have unprovoked thrombotic events — deep vein thrombosis (DVT), pulmonary embolism (PE), or atypical thrombosis — living in high-altitude regions, according to a study published in the International Journal of General Medicine. 

Thrombosis often serves as the initial manifestation of a MPN and is a significant contributor to both morbidity and mortality. JAK2 plays a role in influencing the proliferation of hematopoietic cells and the inflammatory signaling cascade; mutation in JAK2 is notably associated with higher rates of cellular proliferation and differentiation, as well as cytokine release. Patients with MPNs and JAK2 mutations typically have a raised risk of thrombosis when compared with their counterparts who do not have JAK2 mutations.

High-altitude living is associated with alterations in coagulation pathways and blood composition. Studies demonstrate that otherwise healthy individuals with high-altitude hypoxia are at an increased risk of developing idiopathic arterial and venous thrombosis. Scientists suspect that the high altitude can interact with background hereditary/acquired thrombophilia to further exacerbate the risk of initial/recurrent thrombosis.

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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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