Medication Summary
One objective of therapy for polycythemia vera (PV) is to control the myeloproliferative activity of this disease. Evidence of an increase in levels of white blood cells and/or platelets and organomegaly indicate uncontrolled myeloproliferative activity that requires a myelosuppressive agent.
Studies by the Polycythemia Vera Study Group (PVSG) have led to the abandonment of long-term therapy with phosphorus-32 (32P) and most alkylating agents (eg, busulfan, chlorambucil), and to the use of hydroxyurea (HU) instead. However, long-term data seem to indicate a possible slight late increase in cases of acute leukemia in patients with PV who are treated with HU for more than 15 years.
Ruxolitinib is a second-line therapy for patients in whom HU is ineffective or poorly tolerated. It is also approved for use in intermediate- or high-risk myelofibrosis, including primary myelofibrosis, post-PV myelofibrosis, and post–essential thrombocythemia myelofibrosis.
Another JAK inhibitor, fedratinib, is indicated for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis.
Ropeginterferon alfa-2b-njft (Besremi) is indicated for treatment of adults with PV regardless of their treatment history.
Antimetabolites
Class Summary
HU is a nonalkylating agent that inhibits DNA synthesis and cell replication by blocking the enzyme ribonucleoside diphosphate reductase.
Hydroxyurea (Droxia, Hydrea)
Inhibitor of deoxynucleotide synthesis and DOC for inducing hematologic remission in CML. Less leukemogenic than alkylating agents such as busulfan, melphalan, or chlorambucil. Myelosuppressive effects last a few days to a week and are easier to control than those of alkylating agents; busulfan has prolonged marrow suppression and can cause pulmonary fibrosis. Can be administered at higher doses in patients with extremely high WBC counts (>300,000/µL) and adjusted accordingly as counts fall and platelet counts drop. Dose can be administered as a single daily dose or divided into 2-3 doses at higher dose ranges. Droxia, available in smaller tabs of 200, 300, and 400 mg, is for patients with sickle cell disease.
JAK Inhibitors
Class Summary
Myelofibrosis is a myeloproliferative neoplasm known to be associated with dysregulated Janus-associated kinase (JAK) signaling.
Ruxolitinib (Jakafi)
JAK1/JAK2 kinase inhibitor indicated for polycythemia vera in patients who have had an inadequate response to or are intolerant of hydroxyurea. Janus-associated kinases (JAKs) JAK1 and JAK2 mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.
Fedratinib (Inrebic)
Fedratinib inhibits Janus-associated kinase-2 (JAK2), which mediates signaling of cytokines and growth factors that are important for hematopoiesis and immune function. It is indicated for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis.
FGFR Inhibitors
Class Summary
Consider for relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with fibroblast growth factor receptor 1 (FGFR1) rearrangement.
Pemigatinib (Pemazyre)
Orally bioavailable inhibitor of the FGFR types 1, 2, and 3 (FGFR1/2/3). Pemigatinib inhibits FGFR 1/2/3 phosphorylation and signaling, and decreases cell viability in cancer cell lines with activating FGFR amplifications and fusions. It is indicated for relapsed or refractory MLNs in adults with FGFR1 rearrangement.
Imidazole Quinazolines
Class Summary
Imidazole quinazolines have been demonstrated to have powerful anti-aggregating effects on platelets and to cause thrombocytopenia.
Anagrelide hydrochloride (Agrylin)
Primary activity is to lower platelet levels but shows slight decrease in mean hemoglobin and hematocrit while WBC counts maintained. Effective in polycythemia vera with elevated platelet counts. Adjust dosage to lowest effective dose to reduce and maintain platelet counts, WBC count, and hemoglobin levels within reference range.
Interferons
Class Summary
Recombinant interferon alfa is a biologic response modifier with myelosuppressive activity.
Interferon alfa 2b (Interferon alfa-2b, Intron A)
Protein product manufactured by recombinant DNA technology. Can lower counts and shrink enlarged spleens.
Ropeginterferon alfa 2b (Besremi, Ropeginterferon alfa-2b-njft)
Long-acting pegylated interferon alfa-2b. Alfa interferons bind to and activates the human type 1 interferon receptor; signal transduction is initially mediated by the Janus kinase-2 gene (JAK2); polycythemia vera is caused by a JAK2 V617F mutation, that permanently turns of signaling at affected cytokine receptors; this results in overproduction of RBCs by the bone marrow.
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Bone marrow film at 100X magnification demonstrating hypercellularity and increased number of megakaryocytes. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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Blood film at 400X magnification demonstrating polyglobulia and thrombocytosis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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Bone marrow film at 400X magnification demonstrating dominance of erythropoiesis. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
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This blood film at 10,000X magnification shows a giant platelet and an eosinophil. Erythrocytes show signs of hypochromia as a result of repeated phlebotomies. Courtesy of U. Woermann, MD, Division of Instructional Media, Institute for Medical Education, University of Bern, Switzerland.
