Publications by authors named "Verstovsek S"
Article Synopsis
- The study compares the projected costs and time burdens for US patients with myelofibrosis and anemia treated with momelotinib versus danazol, based on data from the MOMENTUM trial and earlier research.
- It indicates that momelotinib leads to significant reductions in transfusion frequency, resulting in lower annual medical costs ($53,143 vs. $46,455) and outpatient transfusion costs ($42,021 vs. $8,370) for transfusion-dependent and independent patients.
- Additionally, patients treated with momelotinib are expected to save an average of 173 hours for transfusion-dependent and 35 hours for transfusion-independent patients, highlighting benefits in both
Background: An inflammatory bone marrow microenvironment contributes to acquired bone marrow failure syndromes. CK0801, an allogeneic T regulatory (Treg) cell therapy product, can potentially interrupt this continuous loop of inflammation and restore hematopoiesis.
Methods: In this phase 1 dose-escalation study of CK0801 Treg cells, we enrolled patients with bone marrow failure syndromes with suboptimal response to their prior therapy to determine the safety and efficacy of this treatment for bone marrow failure syndromes.
Article Synopsis
- Bone marrow fibrosis (BMF) is linked to myelofibrosis and can affect prognosis, but this study explores its relationship with treatment outcomes in patients receiving JAK inhibitors momelotinib and ruxolitinib.
- In a study of patients with BMF, only momelotinib showed increased transfusion independence and hemoglobin levels, while ruxolitinib showed a decrease in hemoglobin.
- The findings suggest that changes in BMF do not correlate with clinical improvements or survival benefits, indicating that BMF may not be an effective surrogate marker for assessing the efficacy of JAK inhibitors.
Article Synopsis
- Polycythemia vera is a chronic blood disorder leading to high red blood cell counts, and rusfertide is a treatment that mimics a hormone controlling iron levels, but its safety and effectiveness in these patients were previously unknown.
- The REVIVE trial tested rusfertide in two parts: a 28-week dose-finding phase involving 70 patients, followed by a 12-week phase where participants received either rusfertide or a placebo.
- Results showed that patients treated with rusfertide had significantly fewer annual phlebotomies (0.6 vs. 8.7) and a better response rate (60% vs. 17%) compared to the placebo group, along with improvements
Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule.
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- - Patients with myelofibrosis suffer from various symptoms due to bone marrow fibrosis and inflammation, and improving these symptoms can enhance their quality of life.
- - This study analyzed data from two phase III trials of momelotinib (SIMPLIFY-1 and SIMPLIFY-2) to determine a meaningful change threshold (MCT) for symptoms, finding it to be 8 points for treatment-naive patients and 6 points for those previously treated.
- - Results showed that momelotinib effectively improved patient symptoms, suggesting that the traditional 50% reduction standard used in clinical trials may be too conservative and that momelotinib offers significant benefits compared to other treatments in myelofibrosis patients.
Reappraisal of cardiovascular risk factors in patients with chronic myeloproliferative neoplasms.
Clin Adv Hematol Oncol
October 2023
Cardiovascular (CV) risk factors are important contributors to thrombotic risk in the general population and in patients with chronic myeloproliferative neoplasms (MPNs). However, the role of CV risk factors is often masked by other disease features that have a strong prognostic impact regarding thrombotic risk in MPN patients. This review summarizes the contemporary knowledge and aspects that have not been addressed or lack consensus in the medical community.
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- Momelotinib, an oral JAK inhibitor, showed positive results in treating intermediate- and high-risk myelofibrosis (MF), benefiting symptoms, spleen size, and anemia.
- Post hoc analyses from three phase 3 studies evaluated momelotinib's effectiveness and safety in patients with low platelet counts (<100 × 10/L), revealing comparable or superior response rates to ruxolitinib, especially in transfusion independence.
- Overall, momelotinib maintained treatment benefits and a consistent safety profile in thrombocytopenic patients, presenting itself as a promising option for managing MF in this population.
Article Synopsis
- Myelofibrosis (MF) is a chronic condition causing severe symptoms, particularly fatigue and anemia, which greatly affect patients' quality of life.
- The JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib has shown promising results in clinical trials, significantly improving both anemia and overall MF-related symptoms compared to danazol.
- The phase 3 MOMENTUM trial confirmed these benefits, with patients on momelotinib experiencing faster and lasting symptom relief, particularly in fatigue and physical functioning, as demonstrated by various patient-reported outcome measures.
Approved fibroblast growth factor receptor (FGFR) inhibitors include erdafitinib, pemigatinib, and futibatinib. We review the most common toxicities associated with FGFR inhibitors and provide practical advice regarding their management. Hyperphosphatemia can be managed with careful monitoring, dose reduction or interruption, a prophylactic low-phosphate diet, and phosphate-lowering therapy.
View Article and Find Full Text PDFIntroduction: Median duration of therapy with the first JAK1/2 inhibitor ruxolitinib (RUX) approved for patients with intermediate or high-risk myelofibrosis (MF) is about 3 years.
Methods: In this retrospective study, we aimed to evaluate clinical features, predictive factors, and outcome of patients presenting to our institution who were able to remain on RUX for ≥5 years (RUX ≥5y, n = 73).
Results: Comparing baseline demographics of patients who remained on RUX ≥5y (n = 73) with patients who were on RUX for 6 months to 3 years (n = 203), we confirmed that patients on RUX ≥5y lacked advanced clinical features at the start of therapy, such as anemia, neutropenia, thrombocytopenia, higher blasts or monocytes.
The exact prognostic role of cardiovascular (CV) risk factors in patients with BCR::ABL1 negative chronic myeloproliferative neoplasms (MPNs) remains unknown as it is often masked by other MPN-related features that bear strong prognostic impact on thrombotic risk. Therefore, current MPN treatment is not primarily guided by presence of CV risk factors. Treatment of CV risk factors in MPN patients usually mirrors that from the general population, despite the fact that CV risk factors in MPNs have their own specificities.
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- - The phase 3 PERSIST-2 study showed that the JAK2/IRAK1 inhibitor pacritinib improved anemia in patients with cytopenic myelofibrosis.
- - Pacritinib was found to inhibit the ACVR1 receptor more effectively than other similar drugs, which is believed to lower hepcidin production and improve anemia.
- - Among patients who were not transfusion independent at the start of the study, a much higher percentage achieved transfusion independence with pacritinib compared to those receiving the best available therapy.
Article Synopsis
- Janus kinase inhibitors (JAKis) like ruxolitinib are standard treatments for symptomatic myelofibrosis but can lead to treatment discontinuation due to disease progression and side effects.
- * The combination of JAKis with BET inhibitors, such as pelabresib, has shown promise in clinical trials, improving spleen volume and total symptom scores in patients with myelofibrosis.
- * An analysis comparing this combination therapy to standard JAKi monotherapy suggests that pelabresib with ruxolitinib may be more effective in treating treatment-naive patients with myelofibrosis.
Article Synopsis
- - The MOMENTUM study successfully showed that momelotinib, compared to danazol, provided significant improvements in symptoms, spleen size, and anemia in myelofibrosis patients at the 24-week mark, and this analysis focuses on outcomes from 24 to 48 weeks.
- - The study involved 107 international sites with adult patients who had a history of myelofibrosis and were treated with a Janus kinase inhibitor, with participants randomly assigned to receive either momelotinib or danazol for 24 weeks.
- - After 24 weeks, all patients transitioned to open-label momelotinib, and this updated analysis reports on the duration of responses and additional patient results through week 48
Patients with polycythemia vera (PV) are at significant risk of thromboembolic events (TE). The PV-AIM study used the Optum de-identified Electronic Health Record dataset and machine learning to identify markers of TE in a real-world population. Data for 82,960 patients with PV were extracted: 3852 patients were treated with hydroxyurea (HU) only, while 130 patients were treated with HU and then changed to ruxolitinib (HU-ruxolitinib).
View Article and Find Full Text PDFMyelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials.
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- Myelofibrosis (MF) has two main phenotypes: myeloproliferative, which generally features higher blood counts and better overall survival, and myelodepletive, marked by cytopenias and worse survival.
- The myeloproliferative phenotype is more often linked to secondary MF and has a simpler mutation profile, while the myelodepletive phenotype relates to primary MF and shows greater genomic complexity and fibrosis.
- Treatment options like Ruxolitinib and fedratinib are tailored to each phenotype, and with advancements in understanding MF diversity, doctors can now provide more personalized care to improve outcomes for patients.
Background: The treatment of patients with myelofibrosis (MF) has evolved in the past decade, as reflected in an increased use of various therapeutic agents that could potentially impact patient outcomes.
Methods: In this retrospective study, the authors evaluated the pattern of therapy and its possible impact on the survival of patients with MF at their institution. Patients (n = 802) with newly diagnosed, chronic, overt MF (MF fibrosis grade ≥2, <10% blasts) seen at their cancer center between 2000 and 2020 were included.