Category Archives: Treatment

Understanding Hematocrit Thresholds in Polycythemia Vera Treatment

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March 19, 2025

Author(s): Maggie L. Shaw, Andrew Kuykendall, MD

In early March, The American Journal of Managed Care® spoke with Andrew Kuykendall, MD, a clinical researcher at Moffitt Cancer Center who focuses on myeloproliferative neoplasms (MPNs), myelodysplastic syndrome/MPN overlap syndromes, and systemic mastocytosis. Kuykendall is an investigator on the phase 3 VERIFY trial (NCT05210790) of the injectable hepcidin mimetic rusfertide (Takeda) to treat polycythemia vera (PV) by enabling patients to achieve and sustain hematocrit control.1 Hematocrit is the measure of the percentage of red blood cells in the body.2

Treatment guidelines in PV currently recommend maintaining hematocrit below 45%, with a higher threshold for men vs women.2 For part 2 of this interview, Kuykendall explains the reasoning behind having different hematocrit thresholds.

In the first part of the interview, Kuykendall discussed how PV manifests and common ways to reduce its negative impact on patient quality of life.

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Optimizing Myelofibrosis Care in the Age of JAK Inhibitors

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Author: Douglas Tremblay, MD

How do you assess a patient’s prognosis at the time that they are diagnosed with myelofibrosis?
In the clinic, we use several scoring systems that have been developed based on the outcomes of hundreds of patients with myeloproliferative neoplasms (MPNs) to try to predict survival from time of diagnosis. Disease features associated with a poor prognosis include anemia, elevated white blood cell count, advanced age, constitutional symptoms, and increased peripheral blasts. Some of these scoring systems also incorporate chromosomal abnormalities as well as gene mutations to further refine prognostication.1

Determining prognosis can be important to creating a treatment plan, particularly to decide if curative allogeneic stem cell transplantation is necessary. However, I always caution patients that these prognostic scoring systems cannot tell the future and that each patient may respond differently to treatment.

How do you monitor for disease progression?
I will discuss with patients how they are feeling in order to determine if there are any new or developing symptoms that could be a sign that their disease is progressing. I will also review their laboratory work looking for changes in blood counts that could be a signal of disease evolution.

For instance, development of anemia or thrombocytopenia may signal worsening bone marrow function or progression to secondary acute leukemia. If there are concerning signs or symptoms, I will then perform a bone marrow biopsy with aspirate that will include assessment of mutations and chromosomal abnormalities to determine if their disease is progressing.

What are the first-line treatment options for a patient newly diagnosed with myelofibrosis, and how do you determine the best course of action?
For patients with myelofibrosis, the first-line treatment options include Janus kinase (JAK) inhibitors, which are effective at improving spleen size and reducing symptom burden. The US Food and Drug Administration (FDA) has approved 4 JAK inhibitors for the treatment of myelofibrosis: ruxolitinib, fedratinib, pacritinib, and momelotinib (Table).2-13 In general, ruxolitinib is the first-line treatment option unless there is thrombocytopenia, in which case pacritinib is more appropriate. In patients with baseline anemia, momelotinib may be the best choice.

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JAK Inhibitors Reduce Thromboembolic Risk in Myeloproliferative Neoplasm Therapy

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March 11, 2025

Author(s): Alex Biese

Fact checked by: Ryan Scott

Treatment with Janus kinase inhibitors (JAKis) has been found to be associated with a reduction in risk of thromboembolic events among patients with myeloproliferative neoplasms (MPNs), according to research findings.

These findings were published in eJHaem, and are driven by observations of treatment with Jakafi (ruxolitinib) for patients with polycythemia vera and myelofibrosis, researchers noted.

“In this meta-analysis, JAKi [used for] MPN [treatment] was associated with a reduced risk of thromboembolic events compared [with] control, primarily driven by studies of [Jakafi] in polycythemia vera and myelofibrosis,” first study author Roberta Dunn and colleagues wrote in the study. “JAKi treatment was not associated with an increased risk of [major adverse cardiovascular events] or hypertension, adding to the existing body of evidence demonstrating the safety of JAKi in the treatment of MPNs. Further prospective clinical trials are warranted to confirm these findings and characterize the cardiovascular profile of other JAKis in all types of MPNs.”

Dunn is a medical student at the School of Medical Education, King’s College London, as well as a student researcher at Guy’s and St Thomas’ NHS Foundation Trust, in the United Kingdom.

MPNs, according to the Cleveland Clinic, are rare blood cancers that involve the patient’s body making too many red blood cells, white blood cells or platelets. JAKis, as explained by the National Cancer Institute, block the actions of enzymes which control cell signaling and growth, the number of blood cells and platelets made in the bone marrow, inflammation, and immune cell activity. Blocking these enzymes may help prevent abnormal blood cells or cancer cells from growing.

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Patients With MF Who Failed Ruxolitinib Treatment May Benefit From Fedratinib

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Özge Özkaya, MSc, PhD
Publish Date

Fedratinib treatment is effective in patients with myelofibrosis (MF) who discontinued ruxolitinib due to treatment failure, according to data from a real-world study published in the scientific journal Future Oncology.

The findings of this study offer a new option for patients with MF whose disease does not respond to ruxolitinib treatment.

To assess the real-world treatment patterns with fedratinib as well as clinical outcomes in patients with primary or secondary MF after ruxolitinib discontinuation, a team of researchers conducted a retrospective, noninterventional medical record review of 196 patients with MF in Germany, Canada, and the United Kingdom.

Data about the patients was provided by 70 physicians of whom 78.6% were primarily hematologists or oncologists.

Of these 196 patients, the majority (76.5%) had primary MF and started treatment with fedratinib at a mean age of 67.7 .

The median duration of treatment with fedratinib was 11.5  months and the median follow-up period was 13.8  months.  Almost half (49.5%) of patients started fedratinib at the dose indicated on the label, i.e. 400  mg per day.

Six months after the start of treatment with fedratinib, 77.7% of patients had symptom response and 66.8% had spleen response.

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Fedratinib Shows Safety, Potential as Post-Transplant Therapy in MPNs

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February 21, 2025

Fedratinib (Inrebic) as a maintenance therapy following allogeneic hematopoietic cell transplant given at a 400 mg daily dose was determined to be safe and established as the maximum tolerated dose (MTD) for patients with myeloproliferative neoplasms (MPNs).1 

Findings come from a recent phase 1 trial where experts explored the potential of fedratinib, a JAK2 inhibitor already approved for pre-transplant myelofibrosis, as a post-transplant maintenance therapy to reduce relapse risk and mitigate graft-vs-host disease (GVHD).

In an interview with Targeted OncologyTM, Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the department of bone marrow transplant and cellular immunotherapy, discussed the trial’s findings, the safety profile of fedratinib, and its evolving role in the post-transplant setting.

Targeted Oncology: Could you discuss the background of this study and what motivated the research?

Elmariah: One of my areas of research is transplant for myelofibrosis and myeloproliferative neoplasms. While transplant can be curative, the cure rate, depending on the study, is generally in the 40% to 60% range. The main reason patients are not cured by transplant is largely the risk of relapse, which [occurs when] the cancer returns after the transplant. For those who do not relapse, there is also the risk of toxicity, such as GVHD, where the transplant attacks the patient’s own body. There are many strategies in development, both for myelofibrosis and other cancers, to reduce the risks of relapse and GVHD.

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Fedratinib in 2025 and Beyond: Indications and Future Applications

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Alexander Coltoff (Medical University of South Carolina, United States) John Mascarenhas (Icahn School of Medicine at Mount Sinai, United States)

Abstract

Dysregulated JAK/STAT signaling underlies the pathogenesis of myelofibrosis, a myeloproliferative neoplasm characterized by cytopenias, splenomegaly and constitutional symptoms. JAK inhibitors, such as fedratinib, are the primary therapeutic option for patients with high-risk or symptomatic myelofibrosis. Fedratinib has characteristics that distinguish it from the other commercially available JAK inhibitors, such as its preferential inhibition of JAK2 and its inhibitory effects on kinases such as FLT3 and BRD4. Fedratinib is most often used in the second-line setting after intolerance or resistance to other JAK inhibitors, but there is substantial evidence that it is an effective first-line option in the appropriate patient population. Prevention and early treatment of fedratinib-related gastrointestinal toxicity is key to maintaining adequate drug exposure, and clinicians must remain vigilant for Wernicke encephalopathy during treatment. Fedratinib’s JAK2 selectivity and kinome profile make it an appealing agent for alternative indications, such as myelodysplastic/myeloproliferative neoplasms and maintenance after bone marrow transplantation, which are under active investigation.

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Second-Line Fedratinib Produces Early Platelet Count Improvements in Myelofibrosis

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February 5, 2025

Author(s): Jax DiEugenio

Fact checked by: Chris Ryan

Patients with myelofibrosis who received second-line fedratinib (Inrebic) experienced early increases in platelet count compared with those given best available therapy (BAT), and a higher magnitude of benefit was observed in patients with a low platelet count at baseline, according to findings from the phase 3 FREEDOM2 trial (NCT03952039) presented at the 2024 ASH Annual Meeting.

Findings showed that in the overall safety population, fedratinib generated improvements in mean platelet count and mean change from baseline platelet count, most noticeably in early treatment cycles.

In patients with a low platelet count at baseline, defined as at least 50 to less than 100 x 109/L, patients treated with fedratinib (n = 34) experienced a mean increase in platelet count of 45% on day 15 of cycle 1 compared with 11% for those given BAT (n = 21). Among patients with a high platelet count at baseline of at least 100 x 109/L, these rates were 27% for fedratinib (n = 85) and –6% for BAT (n = 39).

During a presentation of the data, lead study author Haifa Kathrin Al-Ali, MD, explained that increased platelet count was not correlated with changes in spleen size, pointing to a potential benefit for fedratinib on thrombopoiesis.

“These data suggest a platelet-sparing effect of second-line fedratinib vs BAT, and support fedratinib as a promising second-line treatment option for patient with myelofibrosis with low or high baseline platelet count,” said Al-Ali, who is a professor of translational oncology and head of the Krukenberg Cancer Center at the University Hospital of Halle (Saale) in Germany.

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Real-world treatment patterns and health outcomes for patients with myelofibrosis treated with fedratinib

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January 14, 2025

Francesco Passamonti Shalon Jones e , a,b , Siddhi Korgaonkar c Dorothy Zissler e , , Keith L Davis Rohan C Parikh c c , Manoj Chevli d , and Samantha Slaff

ABSTRACT

Aim: Assess real-world fedratinib (FEDR) treatment patterns and clinical outcomes in patients with primary or secondary myelofibrosis following discontinuation of ruxolitinib (RUX). Patients & Methods: This study was a retrospective, noninterventional medical record review of patients in Canada, Germany, and the United Kingdom (UK). A total of 70 physicians (primarily hematologist-oncologists [78.6%]) provided data for 196 eligible patients.

Results: Patients were mostly male (62.8%) with primary myelofibrosis (76.5%) and initiated FEDR at a mean age of 67.7 years. Median treatment duration was 11.5 months (median follow-up, 13.8 months), and nearly half (49.5%) of patients initiated FEDR at the label-indicated dose of 400 mg daily. Six months post-initiation, 77.7% and 66.8% of patients experienced symptom and spleen response, respectively. Kaplan-Meier estimates of median progression-free and overall survival from initiation were 23.8 months (95% CI, 21.1–27.6) and 29.8 months (95% CI, 23.9-NE), respectively.

Conclusion: These findings demonstrate real-world FEDR effectiveness among patients with myelofibrosis who discontinued RUX.

PLAIN LANGUAGE SUMMARY

What is this summary about?

Myelofibrosis (MF) is a rare blood cancer that can cause unhealthy spleen growth and symptoms, such as feeling tired, loss of appetite, bone pain, and fever. This is a summary of an article that reviewed medical records of patients with MF from treatment centers in Canada, Germany, and the United Kingdom (UK). The study looked at people who had been taking a medication called fedratinib (FEDR) for their MF after they had stopped taking a different medication called ruxolitinib (RUX). Many of the people stopped taking RUX because their MF got worse within a few years. The study wanted to see if taking FEDR reduced symptoms and spleen size for people with MF after they stopped taking RUX.

What were the results?

After at least 6 months of taking FEDR, 77.7% of the people in the study had fewer symptoms, and 66.8% of people in the study had a decrease in spleen size or no spleen growth. Additionally, most people taking FEDR after discontinuing RUX went nearly 2 years without their MF symptoms or illness getting worse.

What do the results mean?

These results suggest that FEDR is an effective treatment for people with MF who have stopped taking RUX.

In Charleston, West Virginia, Tracking MPN Symptoms Becomes a Priority

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January 17, 2025

Author(s): Mary Caffrey

When patients with myeloproliferative neoplasms (MPNs) must travel 2 hours for appointments with a cancer care team, capturing all their symptoms to ensure proper treatment is vital.

So, when Charleston Area Medical Center (AMC) Vandalia Health, located in Charleston, West Virginia, signed on to be part of the Association of Cancer Care Centers (ACCC) MPN Quality Improvement Program, systematic and accurate recording of patients’ symptoms was a priority. In a 12-month period, the cancer program serves 78 patients with polycythemia vera, 111 patients with essential thrombocythemia, and 48 patients with primary myelofibrosis.

Charleston AMC serves a large area in southern West Virginia, including some heavily rural areas. Its team includes general medical oncologists and hematologists who treat all types of cancers, 5 patient navigators, and 2 financial navigators who deal with insurance coverage, transportation issues, and other barriers to access. There is 1 social worker as well as nurses and other team members. Complementing the team are outside partners who help Charleston AMC meet multiple social needs.

As with ACCC Quality Improvement Program participants from Perlmutter Cancer Center at NYU Langone Health and Kent Hospital in Rhode Island, the multidisciplinary team in Charleston West Virginia, first took part in a webinar on MPN patient management.1

The ACCC Quality Improvement program was supported by Incyte.

The Charleston AMC team learned about the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS),2 a validated MPN patient-reported outcome tool that is recommended in the National Comprehensive Cancer Network Guidelines. Patients complete the assessment when they arrive at their appointments, giving providers an overview of symptoms that can be tracked over time.

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Fedratinib for the treatment of myelofibrosis: a critical appraisal of clinical trial and “real-world” data

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January 14, 2025

Adrian Duek, Ilona Leviatan, Osnat Jarchowsky Dolberg & Martin H. Ellis

Abstract

Fedratinib is a predominantly JAK2 inhibitor that has shown efficacy in untreated and ruxolitinib-exposed patients with myelofibrosis (MF). Based on randomized clinical trial data, it is approved for use in patients with International Prognostic Scoring System (IPSS) or Dynamic International Prognostic Scoring System (DIPSS) intermediate-2 or high-risk disease and is distinguished from ruxolitinib in that it can be administered without dose reduction in patients with thrombocytopenia, to a platelet count above 50,000/µL. In these trials, fedratinib achieved significant spleen volume reduction in ~30–45% of patients and improvement in total symptom scores in 35–40% with good tolerability. In contrast, recently published real-world data suggest that these responses may not be as robust outside clinical trials. In the context of routine clinical practice spleen responses are documented in only 13–68%, with varying degrees of symptom improvement. This may be due to the lack of a uniform definition of ruxolitinib failure, which may influence the timing of initiating fedratinib as a second-line treatment and result in a more prolonged exposure to ruxolitinib prior to intitaing fedratinib treatment. We suggest that given the growing number of drugs available for use in MF, recognizing the failure of first-line (and potentially subsequent) treatments is critical to allow timely transition to potentially more active agents, as highlighted by the data pertaining to fedratinib.

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