Medication Summary
Chemotherapeutics have mainly been used as cytoreductive therapy to control leukocytosis, thrombocytosis, or organomegaly. Hydroxyurea is the preferred agent, but other drugs (eg, interferon, cladribine) have also been used. Busulfan has been used, but it is not a preferred agent in view of the lesser toxicity of hydroxyurea. Ruxolitinib is indicated for myelofibrosis and is an effective agent to reduce splenomegaly. Another JAK inhibitor, fedratinib, is indicated for adults with intermediate-2 or high-risk primary myelofibrosis. Patients with primary myelofibrosis are especially prone to developing myelotoxicity with these agents, which should therefore be used with caution.
Antineoplastic Agents
Class Summary
Antineoplastic agents are predominantly used as cytoreductive therapy to control leukocytosis, thrombocytosis, and organomegaly. Patients with primary myelofibrosis are especially prone to developing myelotoxicity with these agents; therefore, use them with caution.
Hydroxyurea (Droxia, Hydrea)
Hydroxyurea is an inhibitor of deoxynucleotide synthesis. It is less leukemogenic than alkylating agents (busulfan) are. Hydroxyurea's myelosuppressive effects last a few days to a week and are easier to control than those associated with alkylating agents. It is lethal to cells in the S phase and is cell-cycle specific.
This agent is used mainly to control counts and alleviate constitutional symptoms or symptoms resulting from hepatic enlargement. It can be administered at higher doses in patients with extremely high WBC counts (>300,000/µL) and adjusted accordingly as WBC and platelet counts fall. Hydroxyurea can be administered as a single daily dose or divided into 2-3 doses at a higher dose range.
Busulfan (Myleran, Busulfex)
Hydroxyurea is an inhibitor of deoxynucleotide synthesis. It is less leukemogenic than alkylating agents (busulfan) are. Hydroxyurea's myelosuppressive effects last a few days to a week and are easier to control than those associated with alkylating agents. It is lethal to cells in the S phase and is cell-cycle specific.
This agent is used mainly to control counts and alleviate constitutional symptoms or symptoms resulting from hepatic enlargement. It can be administered at higher doses in patients with extremely high WBC counts (>300,000/µL) and adjusted accordingly as WBC and platelet counts fall. Hydroxyurea can be administered as a single daily dose or divided into 2-3 doses at a higher dose range.
Cladribine (Leustatin)
Cladribine is a synthetic antineoplastic agent for continuous intravenous (IV) infusion. The enzyme deoxycytidine kinase phosphorylates this compound into active 5'-triphosphate derivative, which then breaks DNA strands and inhibits DNA synthesis. Cladribine disrupts cell metabolism, causing death to resting and dividing cells.
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 treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. 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.
Pacritinib (Vonjo)
Pacritinib is an oral kinase inhibitor with activity against wild type JAK2, mutant JAK2V617F form and FLT3, which contribute to signaling of several cytokines and growth factors that are important for hematopoiesis and immune function. It also inhibits additional cellular kinases (such as CSF1R and IRAK1), clinical relevance of which is unknown. It is indicated for the treatment for adults with myelofibrosis and severe thrombocytopenia (platelet count 9</sup>/L).
Momelotinib (Ojjaara)
Momelotinib, a first-in-class inhibitor of activin A receptor type 1 as well as JAK1 and JAK2, has shown symptom, spleen, and anemia benefits in myelofibrosis. It is indicated for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adults with anemia.
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.
Biological Response Modulators
Class Summary
Immunotherapy (biotherapy) currently used to treat patients with melanoma includes IFN and IL-2.
Interferon alfa-2b (Intron A)
This is a protein product manufactured by recombinant DNA technology. Its mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles. Its immunomodulatory effects include suppression of tumor cell proliferation, enhancement of macrophage phagocytic activity, and augmentation of lymphocyte cytotoxicity.
Peginterferon alfa-2b (Pegintron, Pegintron Redipen, Sylatron)
This is a protein product manufactured by recombinant DNA technology. Its mechanism of antitumor activity is not clearly understood, but direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.
Androgens
Class Summary
Androgens improve symptoms of anemia and decrease transfusion requirements in patients with primary myelofibrosis.
Oxymetholone (Anadrol-50)
Oxymetholone is used to manage anemias resulting from deficient RBC production.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. These agents modify the body's immune response to diverse stimuli.
Prednisone
Prednisone inhibits phagocytosis of platelets and may improve RBC survival.
Prednisolone (Orapred ODT, Prelone, Millipred)
Prednisolone decreases autoimmune reactions, possibly by suppressing key components of the immune system. This agent does not need to undergo hepatic metabolism.
Immunomodulators
Class Summary
Agents in this category may have antiangiogenesis and immunomodulatory effects.
Thalidomide (Thalomid)
Thalidomide's mechanism of action not clearly known, but the drug is thought to work by immunomodulatory effects and antiangiogenesis.
Lenalidomide (Revlimid)
A thalidomide analogue, lenalidomide is an immunomodulatory agent with antiangiogenic and antineoplastic properties.
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Primary myelofibrosis. Peripheral smear shows teardrop red blood cells (RBCs) and a leukoerythroblastic picture with nucleated RBC precursors and immature myeloid cells. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
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Bone marrow biopsy from a patient with primary myelofibrosis shows extensive fibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
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Reticulin stain on a bone marrow biopsy from a patient with primary myelofibrosis shows extensive fibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
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Extramedullary hematopoiesis in the spleen of a patient with primary myelofibrosis. Courtesy of Wei Wang, MD, and John Lazarchick, MD, Department of Pathology, Medical University of South Carolina.
