Moving towards disease modification in polycythemia vera.
Jan Philipp BewersdorfJoan HowLucia MasarovaPrithviraj BoseNaveen PemmarajuJohn O MascarenhasRaajit K RampalPublished in: Blood (2023)
Polycythemia vera (PV) belongs to the BCR-ABL1-negative myeloproliferative neoplasms and is characterized by activating mutations in JAK2 and clinically presents with erythrocytosis, variable degrees of systemic and vasomotor symptoms, and an increased risk of both thromboembolic events and progression to myelofibrosis and acute myeloid leukemia (AML). Treatment selection is based on a patient's age and a history of thrombosis with low-risk PV patients treated with therapeutic phlebotomy and aspirin alone, while cytoreductive therapy with either hydroxyurea or interferon (IFN)-α is added for high-risk disease. However, other disease features such as significant disease-related symptoms and splenomegaly, concurrent thrombocytosis and leukocytosis, or intolerance of phlebotomy can constitute an indication for cytoreductive therapy in otherwise low-risk patients. Additionally, recent studies demonstrating the safety and efficacy (i.e., reduction in phlebotomy requirements and molecular responses) of ropegylated IFN-α-2b support its use in low-risk PV patients. Additionally, emerging data suggest that early treatment is associated with higher rates of molecular responses, which might eventually enable time-limited therapy. Nonetheless, longer follow-up is needed to assess whether molecular responses associate with clinically meaningful outcome measures such as thrombosis and progression to myelofibrosis or AML. In this review, we provide an overview of the current and evolving treatment landscape of PV and outline our vision for a patient-centered, phlebotomy-free, treatment approach using time-limited, disease-modifying treatment modalities early in the disease course, which could ultimately impact the natural history of the disease.
Keyphrases
- acute myeloid leukemia
- end stage renal disease
- squamous cell carcinoma
- ejection fraction
- newly diagnosed
- stem cells
- acute coronary syndrome
- cardiovascular disease
- radiation therapy
- signaling pathway
- pulmonary embolism
- machine learning
- acute lymphoblastic leukemia
- prognostic factors
- cardiovascular events
- allogeneic hematopoietic stem cell transplantation
- artificial intelligence
- percutaneous coronary intervention
- cell therapy
- locally advanced
- patient reported
- chronic myeloid leukemia