Review
Oncology
Naveen Pemmaraju, Srdan Verstovsek, Ruben Mesa, Vikas Gupta, Jacqueline S. Garcia, Joseph M. Scandura, Stephen T. Oh, Francesco Passamonti, Konstanze Dohner, Adam J. Mead
Summary: This article discusses the definition of disease modification in myelofibrosis and the recent clinical trials of developing therapeutic drugs, emphasizing the need for surrogate measures of survival in early-stage trials.
Review
Biochemistry & Molecular Biology
Mariarita Spampinato, Cesarina Giallongo, Alessandra Romano, Lucia Longhitano, Enrico La Spina, Roberto Avola, Grazia Scandura, Ilaria Dulcamare, Vincenzo Bramanti, Michelino Di Rosa, Nunzio Vicario, Rosalba Parenti, Giovanni Li Volti, Daniele Tibullo, Giuseppe A. Palumbo
Summary: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by clonal proliferation of hematopoietic stem cells leading to bone marrow fibrosis. The main consequences of PMF include neoangiogenesis, megakaryocytes hyperplasia, extensive bone marrow fibrosis, osteosclerosis, and bone damage. The involvement of cytokines, growth factors, and resident cells in the bone marrow microenvironment are linked to disease progression in PMF.
Article
Veterinary Sciences
Amelia G. Campbell, Davis M. Seelig, Joan D. Beckman, Katie M. Minor, Daniel A. Heinrich, Steven G. Friedenberg, Jaime F. Modiano, Eva Furrow
Summary: The study suggests that somatic variants may play a role in the development and perpetuation of myelofibrosis in dogs. Clonal hematopoiesis with increasing incidence with age, as observed in humans, was also found in dogs.
JOURNAL OF VETERINARY INTERNAL MEDICINE
(2022)
Review
Cell Biology
Nicola Polverelli, Mirko Farina, Mariella D'Adda, Enrico Damiani, Luigi Grazioli, Alessandro Leoni, Michele Malagola, Simona Bernardi, Domenico Russo
Summary: Moving from indication to transplantation is a critical process in managing myelofibrosis patients. This review focuses on identifying suitable candidates for transplantation using disease-specific prognostic scores and evaluating their eligibility based on performance, comorbidity, and other combined tools. The review also discusses the importance of pre-transplant management in achieving successful engraftment and reducing non-relapse mortality and relapse incidence. Topics such as managing splenomegaly, constitutional symptoms, cytopenias, iron overload, and choosing the right donor and conditioning regimens are comprehensively explored. The aim of this review is to provide practical guidance for managing myelofibrosis patients who may undergo allo-HCT.
Review
Biochemistry & Molecular Biology
Ana Belen Azuaga, Julio Ramirez, Juan D. D. Canete
Summary: Psoriatic arthritis is a chronic inflammatory disease associated with psoriasis and other comorbidities. Its complex pathogenesis involves genetic predisposition, environmental factors, and immune system activation. Research has identified therapeutic targets based on immune-inflammatory pathways, but heterogeneous responses remain a challenge. Translational research and integration of omics technologies are needed to improve outcomes and identify new targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Health Care Sciences & Services
Dahniel Sastow, Douglas Tremblay
Summary: Myelofibrosis is a hematologic malignancy characterized by abnormal proliferation of myeloid cells and pro-inflammatory cytokine release. JAK inhibitors have revolutionized MF therapy, but their efficacy in reducing leukemic transformation and improving survival is debated. New drugs, such as pacritinib and momelotinib, are being developed to address the cytopenias associated with early JAK inhibitors. Ongoing and future clinical trials are crucial for advancing the field and expanding therapeutic options for MF patients.
THERAPEUTICS AND CLINICAL RISK MANAGEMENT
(2023)
Article
Hematology
Yunfan Yang, Hongmei Luo, Yuhuan Zheng, Zhongqing Zou, Ting Niu, Yongqian Jia, Huanling Zhu, Ting Liu, Yu Wu, Hong Chang, Jie Ji, Jian Li, Ling Pan
Summary: The study aimed to investigate the effect of low-dose ruxolitinib treatment on myelofibrosis (MF), revealing that low-dose treatment resulted in gradual spleen response and significant improvement in bone marrow fibrosis.
ANNALS OF HEMATOLOGY
(2021)
Article
Oncology
Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Naval G. Daver, Koji Sasaki, Helen T. Chifotides, Lingsha Zhou, Hagop M. Kantarjian, Zeev Estrov, Srdan Verstovsek
Summary: This retrospective study evaluated the impact of different therapies on the survival of patients with myelofibrosis. The results showed that treatment with the JAK inhibitor ruxolitinib improved patient outcomes. Approximately 61% of patients initiated MF-directed therapy, with ruxolitinib being the most common choice. About 32% of patients required second-line therapy.
Article
Endocrinology & Metabolism
Michele Dello Spedale Venti, Biagio Palmisano, Samantha Donsante, Giorgia Farinacci, Flavia Adotti, Ilenia Coletta, Marta Serafini, Alessandro Corsi, Mara Riminucci
Summary: This study analyzed the morphological and immunophenotypic changes of bone marrow adipocytes (BMAds) in different types of bone marrow cancers. The results showed that BMAds were significantly reduced in both bone marrow metastasis and myeloproliferative neoplasia with grade-3 myelofibrosis, along with a decrease in cell diameter and area. Additionally, the expression of certain markers in BMAds differed in these two types of cancers.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Hematology
Nicola Polverelli, Elena M. Elli, Elisabetta Abruzzese, Giuseppe A. Palumbo, Giulia Benevolo, Mario Tiribelli, Massimiliano Bonifacio, Alessia Tieghi, Giovanni Caocci, Mariella D'Adda, Micaela Bergamaschi, Gianni Binotto, Florian H. Heidel, Francesco Cavazzini, Monica Crugnola, Novella Pugliese, Costanza Bosi, Alessandro Isidori, Daniela Bartoletti, Giuseppe Auteri, Roberto Latagliata, Lisa Gandolfi, Bruno Martino, Luigi Scaffidi, Daniele Cattaneo, Fabio D'Amore, Malgorzata M. Trawinska, Rossella Stella, Uros Markovic, Lucia Catani, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Massimo Breccia, Domenico Russo, Michele Cavo, Alessandra Iurlo, Francesca Palandri
Summary: RUX treatment has been associated with a higher incidence of SPMs, with NMSCs being the most common. Risk factors for SPMs include male sex and thrombocytosis at RUX start. For SPMs excluding NMSCs, male sex, thrombocytosis, and previous arterial thromboses are considered high-risk factors.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Aniket Bankar, Shabbir Alibhai, Elliot Smith, Dongyang Yang, Sarah Malik, Verna Cheung, Nancy Siddiq, Jaime Claudio, Andrea Arruda, Hubert Tsui, Jose-Mario Capo-Chichi, James A. Kennedy, Caroline McNamara, Hassan Sibai, Dawn Maze, Wei Xu, Vikas Gupta
Summary: Frailty is associated with shorter overall survival and increased JAK inhibitor therapy failure in patients with myelofibrosis, suggesting that higher frailty scores may be a more superior indicator of fitness compared to age, comorbidities, and performance status.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Endocrinology & Metabolism
Marta Kamalska, Marek Karczewski, Evridiki Tsoureli Nikita, Sara Poggiali, Olisova Yu Olisova, Konstantin M. Lomonosov, Torello Lotti
Summary: This review presents mechanisms and new agents for vitiligo treatment, including JAK inhibitors, Wnt response inhibitors, microRNAs, rapamycin, and cytokine-targeted treatments. Vitiligo is a systemic disease requiring both systemic and local treatments. JAK inhibitors, especially when combined with phototherapy, show promise as the most effective treatment. CD8+ T lymphocytes and CD4+ T helper lymphocytes are involved in vitiligo development. Other factors such as ER stress and GRP78 activation, and adhesion deficit are also relevant.
JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS
(2023)
Article
Cell Biology
Taghi Manshouri, Ivo Veletic, Ping Li, C. Cameron Yin, Sean M. Post, Srdan Verstovsek, Zeev Estrov
Summary: GF1 is highly expressed in BM fibrocytes of MF patients, affecting fibrocyte-induced BM fibrosis by influencing MMP levels, and STAT3-activated GLI1 is also involved in the fibrosis process.
CELL DEATH & DISEASE
(2022)
Article
Oncology
John Mascarenhas, Rami S. Komrokji, Francesca Palandri, Bruno Martino, Dietger Niederwieser, Andreas Reiter, Bart L. Scott, Maria R. Baer, Ronald Hoffman, Olatoyosi Odenike, Alessandro M. Vannucchi, Jacqueline Bussolari, Eugene Zhu, Esther Rose, Laurie Sherman, Souria Dougherty, Libo Sun, Fei Huang, Ying Wan, Faye M. Feller, Aleksandra Rizo, Jean-Jacques Kiladjian
Summary: Imetelstat, a telomerase inhibitor, showed potential clinical benefits in symptom response rate for patients with myelofibrosis who are relapsed or refractory to JAK inhibitors. The drug demonstrated longer overall survival, bone marrow fibrosis improvement, and reduction in driver mutations, indicating selective effects on the malignant clone.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Review
Oncology
Francesco Passamonti, Claire N. Harrison, Ruben A. Mesa, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek
Summary: This review provides an overview of current and emerging treatments for anemia in myelofibrosis, including drug therapies and stem cell transplantation. Effective treatments for myelofibrosis-related anemia are currently limited, but new drugs and combination therapies may offer promising treatment options.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Article
Hematology
Srdan Verstovsek, Naveen Pemmaraju, Nancy L. Reaven, Susan E. Funk, Tracy Woody, Frank Valone, Suneel Gupta
Summary: Polycythemia vera (PV), a type of myeloproliferative neoplasm, has an increased risk of thrombotic events (TE) and mortality. Treatment interventions, such as phlebotomy and cytoreductive medications, aim to maintain hematocrit levels below 45% for better outcomes. A retrospective observational study including 28,306 PV patients found that a majority of both high- and low-risk patients initiated treatment with phlebotomy monotherapy, but hematocrit control was suboptimal in both risk groups. Around 16% of individuals experienced at least 1 TE after treatment initiation, suggesting that current PV treatments may not be fully utilized.
ANNALS OF HEMATOLOGY
(2023)
Review
Oncology
Helen T. Chifotides, Lucia Masarova, Srdan Verstovsek
Summary: The development of MF therapeutics has achieved remarkable progress, with JAK2 inhibitors playing a transformative role in MPN treatment. In addition to these inhibitors, there are numerous novel monotherapies and rational combinations being developed to address different aspects of the disease. These advancements have the potential to improve patient outcomes and lead to a golden era in MF treatment.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Pathology
Yahya A. Al-Ghamdi, Jonathan Lake, Adam Bagg, Beenu Thakral, Sa A. Wang, Carlos Bueso-Ramos, Lucia Masarova, Srdan Verstovsek, Heesun J. Rogers, Eric D. Hsi, Jonathon H. Gralewski, Devon Chabot-Richards, Tracy I. George, Anton Rets, Robert P. Hasserjian, Olga K. Weinberg, Megan Parilla, Daniel A. Arber, Osvaldo Padilla, Attilio Orazi, Wayne Tam
Summary: This study compared the pathological and genetic characteristics between triple-negative primary myelofibrosis (TN-PMF) and PMF with canonical driver mutations (DM-PMF). The results showed that TN-PMF patients were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow of TN-PMF patients showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis revealed a higher incidence of trisomy 8, and targeted next-generation sequencing identified a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. These findings suggest that TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.
Review
Hematology
Nicola Polverelli, Juan Carlos Hernandez-Boluda, Tomasz Czerw, Tiziano Barbui, Mariella D'Adda, Hans Joachim Deeg, Markus Ditschkowski, Claire Harrison, Nicolaus Martin Kroger, Ruben Mesa, Francesco Passamonti, Francesca Palandri, Naveen Pemmaraju, Uday Popat, Damiano Rondelli, Alessandro Maria Vannucchi, Srdan Verstovsek, Marie Robin, Antonio Colecchia, Luigi Grazioli, Enrico Damiani, Domenico Russo, Jessica Brady, David Patch, Slawomir Blamek, Gandhi Laurent Damaj, Patrick Hayden, Donal P. McLornan, Ibrahim Yakoub-Agha
Summary: Splenomegaly is a common complication in myelofibrosis patients and can negatively impact outcomes of allogeneic hematopoietic cell transplantation (HCT). This Position Paper provides a shared position statement on the management of splenomegaly before HCT. The assessment, prevalence, and clinical significance of splenomegaly are discussed, along with the need for therapeutic intervention. Specific scenarios, such as splanchnic vein thrombosis and COVID-19, are also addressed.
LANCET HAEMATOLOGY
(2023)
Review
Hematology
Srdan Verstovsek
Summary: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by mutations (most frequently in JAK2, CALR, or MPL), burdensome symptoms, splenomegaly, cytopenia, and shortened life expectancy. In addition to other clinical manifestations, patients with MF often develop anemia, which can either be directly related to MF pathogenesis or a result of MF treatment with Janus kinase (JAK) inhibitors, such as ruxolitinib and fedratinib. This review provides detailed treatment and patient management approaches for both types of anemia presentations in MF and offers recommendations for the treatment of MF in the presence of anemia.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Naval G. Daver, Koji Sasaki, Helen T. Chifotides, Lingsha Zhou, Hagop M. Kantarjian, Zeev Estrov, Srdan Verstovsek
Summary: This retrospective study evaluated the impact of different therapies on the survival of patients with myelofibrosis. The results showed that treatment with the JAK inhibitor ruxolitinib improved patient outcomes. Approximately 61% of patients initiated MF-directed therapy, with ruxolitinib being the most common choice. About 32% of patients required second-line therapy.
Article
Oncology
Srdan Verstovsek, Jean-Jacques Kiladjian, Alessandro M. M. Vannucchi, Ruben A. A. Mesa, Peg Squier, J. E. Hamer-Maansson, Claire Harrison
Summary: This study analyzed the impact of the timing of ruxolitinib treatment on clinical outcomes in patients with intermediate-2 and high-risk myelofibrosis. The results showed that patients who initiated treatment earlier had better outcomes in terms of thrombocytopenia and anemia, higher spleen volume response, and longer overall survival.
Review
Pharmacology & Pharmacy
Pankit Vachhani, Srdan Verstovsek, Prithviraj Bose
Summary: Cytopenic myelofibrosis is a subtype of myelofibrosis characterized by low blood counts, lower driver mutation allele burden, increased likelihood of occurring de novo, greater genomic complexity, worse survival, and higher rates of leukemic transformation. Several JAK inhibitors are available for clinical use, including pacritinib and momelotinib, which show promise in improving cytopenias. These newer JAK inhibitors may become the foundation for future combination therapies.
EXPERT OPINION ON PHARMACOTHERAPY
(2023)
Article
Oncology
John Mascarenhas, Marina Kremyanskaya, Andrea Patriarca, Francesca Palandri, Timothy Devos, Francesco Passamonti, Raajit K. Rampal, Adam J. Mead, Gabriella Hobbs, Joseph M. Scandura, Moshe Talpaz, Nikki Granacher, Tim C. P. Somervaille, Ronald Hoffman, Marielle J. Wondergem, Mohamed E. Salama, Gozde Colak, Jike Cui, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Natalia Curto-Garcia, Claire Harrison, Vikas Gupta
Summary: In patients with myelofibrosis who are naive to JAKi treatment, the rational combination of the BET inhibitor pelabresib and ruxolitinib showed good tolerability and durable improvements in spleen and symptom burden.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Naveen Pemmaraju, Prithviraj Bose, Raajit Rampal, Aaron T. Gerds, Angela Fleischman, Srdan Verstovsek
Summary: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, abnormal cytokine expression, cytopenias, and progressive bone marrow fibrosis. Ruxolitinib, an oral Janus kinase (JAK) 1 and JAK2 inhibitor, was the first approved agent for MF and has revolutionized the treatment approach. The understanding of MF has improved significantly due to targeted JAK1/JAK2 inhibition and extensive literature on ruxolitinib, leading to better management strategies and discussion on future treatment options.
LEUKEMIA & LYMPHOMA
(2023)
Article
Hematology
Ivan Krecak, Marko Skelin, Srdan Verstovsek
Summary: Interferons (IFNs) have been used for decades to treat polycythemia vera (PV). Single-arm clinical trials have shown high hematological and molecular response rates with IFNs, indicating potential disease-modifying activity. However, discontinuation rates of IFNs have been rather high due to frequent treatment-related side-effects.
EXPERT REVIEW OF HEMATOLOGY
(2023)
Review
Hematology
Rodrick Babakhanlou, Srdan Verstovsek, Naveen Pemmaraju, Cristhiam M. M. Rojas-Hernandez
Summary: Erythrocytosis is characterized by elevated hemoglobin and hematocrit levels. It can be classified as primary or secondary, with primary erythrocytosis resulting from a clonal disorder in the bone marrow and secondary erythrocytosis being caused by external stimuli. This review focuses on secondary erythrocytosis, discussing its causes, clinical presentation, and diagnostic and therapeutic approaches.
EXPERT REVIEW OF HEMATOLOGY
(2023)
Review
Oncology
Srdan Verstovsek, Ruben A. Mesa, Robert A. Livingston, Wilson Hu, John Mascarenhas
Summary: Myelofibrosis is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been approved for the treatment of intermediate or high-risk MF patients. It remains the standard of care for higher-risk MF, and dose optimization and management are crucial for maximizing its benefits.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Hematology
Vikas Gupta, John Mascarenhas, Marina Kremyanskaya, Raajit K. Rampal, Moshe Talpaz, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Gozde Colak, Debarshi Dey, Claire Harrison
Summary: A study suggests that pelabresib in combination with ruxolitinib may have higher efficacy in treating JAKi treatment-naive MF patients compared to JAKi monotherapy, with significant improvements in spleen volume reduction and total symptom scores.
Article
Hematology
Srdan Verstovsek, Ruben Mesa, Vikas Gupta, David Lavie, Viviane Dubruille, Nathalie Cambier, Uwe Platzbecker, Marek Hus, Blanca Xicoy, Stephen T. Oh, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Aaron Gerds, Miklos Egyed, Jiri Mayer, Tomasz Sacha, Jun Kawashima, Marc Morris, Mei Huang, Claire Harrison
Summary: Momelotinib is a first-in-class inhibitor of Janus kinases 1 and 2, as well as activin A receptor type 1, and has shown efficacy in addressing the symptoms of myelofibrosis, such as splenomegaly, constitutional symptoms, and anemia. This long-term analysis of pooled data from three phase 3 studies demonstrated the safety and tolerability of momelotinib, with no evidence of long-term or cumulative toxicity. The most common adverse events were diarrhea and hematologic abnormalities, but they were generally manageable. This analysis provides valuable evidence supporting the use of momelotinib in the treatment of myelofibrosis.