Tag Archives: pacritinib

Pacritinib Demonstrates Efficacy, Tolerability in Patients with Myelofibrosis and Thrombocytopenia

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October 16, 2024

Author(s): Alexandra Gerlach, Associate Editor

Pacritinib (Vonjo; CTI BioPharma Corp) demonstrated improved spleen volume reduction (SVR) and was tolerable in patients with myelofibrosis (MF) and thrombocytopenia, according to data published in the European Journal of Hematology. The findings offer deeper insights into the capabilities of Janus kinase (JAK) inhibitors to improve SVR and overall survival (OS), contradicting prior studies advising against use of JAK inhibitors for thrombocytopenia.1

Further studies are needed to identify the long-term safety and efficacy of the therapy.

Image Credit: © AkuAku – stock.adobe.com

Thrombocytopenia, a condition that occurs when blood platelet counts are too low, is a disease-related feature of MF that leads to poorer prognoses impacting both OS and leukemia-free survival. It can be caused by a variety of factors including ineffective hematopoiesis, splenic sequestration, and treatment-related effects. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curable treatment for MF but is only available for a minority of patients. However, the development of JAK inhibitors has expanded treatment options for patients with MF and may show promise for treatment of thrombocytopenia.2

Pacritinib is a JAK inhibitor used to treat intermediate or high-risk MF that targets JAK2 and FMS-like tyrosine kinase 3. It was approved by the FDA in 2022 for treatment of both primary and secondary MF in patients with platelet counts < 50 x 109/L. In the phase 3, randomized, controlled PERSIST-2 trial (NCT02055781), pacritinib demonstrated favorable efficacy and tolerability compared with best available therapy (BAT) in patients with MF and thrombocytopenia.3-5

In the study, approximately 300 patients with thrombocytopenia and primary or secondary myelofibrosis were randomized in a 1:1:1 ratio to receive either pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or BAT. The primary end points included SVR of ≥ 35% reduction in spleen volume from baseline to week 24 as measured by MRI or computed tomography, as well as ≥ 50% reduction in the total symptom score from baseline to week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.1,5

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Bose’s Guide to Ruxolitinib, Fedratinib, Pacritinib, and Momelotinib

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By Prithviraj Bose, MD

Prithviraj Bose, MD, professor in the Department of Leukemia at MD Anderson Cancer Center, provides an overview of the different JAK inhibitors currently available for patients with myeloproliferative neoplasms.

Transcription:

0:09 | We have 4 JAK inhibitors approved for the treatment of myelofibrosis in the US. Important to note, pacritinib [Vonjo] is not approved outside the US. There is obviously a lot to say on this topic, especially, ruxolitinib [Jakafi] was approved in 2011, fedratinib [Inrebic] in 2019 and then pacritinib and momelotinib [Ojjaara], more recently, 2022 and 2023. But I think I will just hit some high points.

0:36 | So for ruxolitinib, the first thing I would say about that is that it is the JAK inhibitor with the most clearly demonstrated survival benefit in myelofibrosis. Now, is that an effect just of ruxolitinib and not of the others? We do not know that. It could be a class effect, but the data are the data and the data are that ruxolitinib is the one that has a clearly shown survival benefit. I think that needs to be considered as we use it, and it is usually the most frequently used frontline drug. Now, where you can get into trouble with ruxolitinib is with cytopenias, low blood counts, and this is a drug that you need to be able to dose well in order to get the benefit that you are seeking. The dose can get compromised by cytopenias.

1:29 | That is where I will tie that into the entry of pacritinib and momelotinib. These are easier to use in the setting of cytopenias. In fact, pacritinib has a label for platelets than 50, and momelotinib is for patients with anemia in myelofibrosis. So right there, you can see that they sort of have their place more in that cytopenic population, which could be frontline, or, more commonly, second-line, after ruxolitinib. I think those are great additions in the sense that you can give them at good doses despite low blood counts, which becomes difficult with ruxolitinib, like I just said. [They are] certainly very welcome additions to the arsenal.

2:12 | I will just say 1 last thing about fedratinib, which was the second one approved. This is a good drug, perhaps as good as ruxolitinib from an efficacy stand point, but really with no clear advantage over ruxolitinib. So, I do not use it in the frontline. I do use it, however, in post-ruxolitinib settings, where the blood counts are good. In those proliferative scenarios, as opposed to the cytopenic scenarios, in second-line and beyond, I do find fedratinib to be a useful drug. It has some toxicities that one has to pay attention to. All patients should get thiamine supplementation, stuff like that, but overall, I would say those are the kind of very high level points about the 4 drugs.

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Vonjo Improves Thrombocytopenia, Anemia in Patients With Myelofibrosis

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By Jax DiEugenio
Fact checked by Chris Ryan

Improvements in thrombocytopenia and anemia were observed in patients with myelofibrosis treated with Vonjo (pacritinib) in the real-world setting, as demonstrated in findings from a retrospective study presented at the 2024 SOHO Annual Meeting.

According to the National Cancer Institute, thrombocytopenia refers to a condition in which patients have a lower-than-normal number of platelets in the blood, and this can result in excessive bleeding from wounds and easy bruising. Anemia is a condition when patients have a low count of red blood cells.

Findings showed that patients with a platelet count below 100 x 109/L (which is considered low) at baseline (74 patients) experienced an early increase in platelet count following treatment initiation that was maintained throughout the observation period. Additionally, an early increase in median hemoglobin (a protein inside red blood cells that carries oxygen from lungs to tissues and organs) was reported in all patients, and this increase was sustained throughout the observation period. Patients with hemoglobin level of less than 8 g/dL (a level that indicates anemia) at the start of treatment (35 patients) experienced a hemoglobin increase of nearly 1 g/dL by day 30.

Notably, patients who received prior treatment with Jakafi (ruxolitinib; 69 patients) experienced an increase in platelet counts and hemoglobin levels following initiation of Vonjo. At baseline, the median platelet count and median hemoglobin level in this population was 91 x 109/L and 8.7 g/dL, respectively. At day 360, the median platelet count and median hemoglobin were 97 x 109/L and 10.4 g/dL, respectively.

“In addition to spleen and symptom benefits observed in previous clinical trials, real-world outcomes demonstrate stability or improvement in thrombocytopenia and/or anemia in patients with myelofibrosis treated with [Vonjo],” lead study author Michael Marrone and colleagues, wrote in a poster presentation of the data. Marrone is an assistant professor in the College of Medicine, Department of Public Health Sciences, at the Medical University of South Carolina in Charleston.

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Real-World Data for Pacritinib Show Improvement in Thrombocytopenia, Anemia in Myelofibrosis

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September 10, 2024

Author(s): Jax DiEugenio

Fact checked by: Chris Ryan

Pacritinib (Vonjo) generated improvements in thrombocytopenia and anemia in patients with myelofibrosis treated in the real-world setting, according to data from a retrospective study presented at the 2024 SOHO Annual Meeting.1

Findings showed that patients with a platelet count below 100 x 109/L at baseline (n = 74) experienced an early increase in platelet count following treatment initiation that was maintained throughout the observation period. Additionally, an early increase in median hemoglobin was reported in all patients, and this increase was sustained throughout the observation period. Patients with hemoglobin level of less than 8.0 g/dL at the start of treatment (n = 35) experienced a hemoglobin increase of nearly 1 g/dL by day 30.

Notably, patients who received prior treatment with ruxolitinib (Jakafi; n = 69) experienced an increase in platelet counts and hemoglobin levels following initiation of pacritinib. At baseline, the median platelet count and median hemoglobin level in this population was 91.0 x 109/L and 8.7 g/dL, respectively. At day 360, the median platelet count and median hemoglobin were 97.0 x 109/L and 10.4 g/dL, respectively.

“In addition to spleen and symptom benefits observed in previous clinical trials, real-world outcomes demonstrate stability or improvement in thrombocytopenia and/or anemia in patients with myelofibrosis treated with pacritinib,” lead study author Michael Marrone, PhD, MPH, and colleagues, wrote in a poster presentation of the data. Marrone is an assistant professor in the College of Medicine, Department of Public Health Sciences, at the Medical University of South Carolina in Charleston.

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Talazoparib Plus Pacritinib Aims to Improve the Limitations of Second-Line Therapy in MPNs

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September 5, 2024

Author(s): Caroline Seymour

Fact checked by:Kristi Rosa

The combination of talazoparib (Talzenna) and pacritinib (Vonjo) could provide more than symptom burden relief for patients with myeloproliferative neoplasms (MPNs) who have become unresponsive to frontline JAK2 inhibition with ruxolitinib (Jakafi), according to Peter Abdelmessieh, DO, MSC.

The regimen is under study in a phase 1 trial (NCT06218628) at Fox Chase Cancer Center and is supported by earlier work published in Blood showing the synergistic disease-modifying activity of the regimen.1

To be eligible for enrollment, patients must have received a diagnosis of histologically or cytologically confirmed primary myelofibrosis, post-polycythemia vera-myelofibrosis, post-essential thrombocythemia-myelofibrosis, chronic myelomonocytic leukemia, polycythemia vera, or essential thrombocytosis according to the 2008 World Health Organization criteria. Patients must also have at least 2 symptoms with a score of 3 or greater or a total score of 12 or greater, according to the Myelofibrosis Symptom Assessment Form v4.0; intermediate-2 or high-risk myelofibrosis according to the Dynamic International Prognostic Scoring System Plus; and a baseline QTc less than 0.47 seconds per Bazett formula.

Additionally, patients must have prior exposure to a JAK2 inhibitor for at least 12 weeks with documented disease progression or have new, palpable splenomegaly measuring at least 5 cm below the left costal margin in patients who had no evidence of splenomegaly before the start of any frontline JAK2 inhibitor.2

“Second-line treatment for patients with this disease is an unmet need along with the need to investigate other possible pathways that might be effective in this disease. The tool shed is essentially barren for clinicians outside of JAK2 inhibitors,” Abdelmessieh said in an interview with OncLive®.

In the interview, Abdelmessieh, an assistant professor in the Department of Bone Marrow Transplant and Cellular Therapies at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, discussed the basis for the phase 1 trial in patients with MPNs.

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Sobi to present new myelofibrosis data at the ASCO 2024 Annual Meeting

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WALTHAM, Mass., May 24, 2024 (GLOBE NEWSWIRE) — Sobi North America, the North American affiliate of Swedish Orphan Biovitrum AB (Sobi®), today announced the presentation of three abstracts that highlights data from its myelofibrosis treatment option at the American Society of Clinical Oncology (ASCO) Annual Meeting taking place in Chicago from May 31 – June 4, 2024.

Sobi’s commitment to delivering innovative treatments for people living with hematological diseases is seen in global studies spanning multiple rare disorders, including myelofibrosis.

A retrospective analysis will be presented that demonstrates the efficacy of pacritinib in spleen volume reduction, symptom benefit and red blood cell transfusion response, compared with best available therapy, in patients with myelofibrosis who have both thrombocytopenia and anemia.

An additional retrospective analysis will be presented that shows the substantial symptom benefit pacritinib provides compared with best available therapy or low-dose ruxolitinib, specifically in patients who required red blood cell transfusion at the time of pacritinib initiation. The number of patients experiencing treatment emergent Grade 3 anaemia was similar between pacritinib and BAT groups.

New real-world data will be presented that demonstrates treatment with pacritinib provides stability or improvement in thrombocytopenia and/or anemia in patients with myelofibrosis, regardless of baseline counts, and has favorable overall survival similar to other JAK inhibitor historical controls.

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How the PERSIST-2 Results Show The Benefit of Pacritinib in MF

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Targeted Oncology Staff

Targeted Oncology: What was the make-up of the PERSIST-2 trial (NCT02055781) looking at pacritinib (Vonjo) in patients with myelofibrosis (MF)?

JOHN MASCARENHAS, MD: This was the more interesting of the 2 PERSIST studies. PERSIST-2 looked at patients with platelets of 100,000/µL or less.1 So, the cytopenic patient with MF could have been given a Janus kinase [JAK] inhibitor before being enrolled, and half did in this study…but these are patients that were hard to treat, which was opposite to the set-up of the COMFORT-1 [NCT00952289] and COMFORT-2 [NCT00934544] studies.2 [Patients in PERSIST-2 study] were given either 400 mg daily or 200 mg of twice daily pacritinib vs patients on best available therapy [BAT], which could also include ruxolitinib [Jakafi], with a coprimary end point of spleen volume reduction of 35% or more and reduction of the total symptom score at week 24.1

What stood out among patients enrolled in either arm of the study?

I think what’s important to appreciate is when asking the investigator what they would give to patients who were randomly assigned to the BAT arm is that there is a lack of options available. In the BAT arm, 45% of patients got low-dose ruxolitinib, 19% had no options, while some patients were getting hydroxyurea [19%], steroids [13%], and even interferons [2%], which I would argue don’t work in this setting.1 These were patients who had higher-risk disease, and half of them had hemoglobin counts less than 10 g/dL, and the median platelet count was somewhere around 50,000/µL [in a majority of patients in both arms].

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