Waldenstrom Macroglobulinemia Medication
- Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD more...
Various drugs, including corticosteroids (eg, prednisone), alkylating agents (eg, chlorambucil, melphalan, cyclophosphamide), biologic response modifiers (eg, interferon alfa, interferon gamma), and purine analogues (eg, fludarabine, 2-chlorodeoxyadenosine), are used in the treatment of Waldenström macroglobulinemia.
Salvage therapy for patients with resistant disease or relapse includes reuse or alternative use of front-line agent, combination therapy, thalidomide (with or without steroids), autologous transplantation, and monoclonal antibody (alemtuzumab).
These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.
Prednisone is an immunosuppressant used for the treatment of autoimmune disorders. It may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity.
Antineoplastics, Tyrosine Kinase Inhibitor
Tyrosine kinase enzymes are responsible for activating many proteins by signal transduction cascades, phosphorylation, and other mechanisms. Tyrosine kinase inhibitors block these functions.
Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor. It forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. BTK's role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell trafficking, chemotaxis, and adhesion. It is the first FDA-approved drug that is indicated for Waldenström macroglobulinemia.
These agents inhibit cell growth and proliferation. Many combinations of chemotherapeutic agents have been tried, with no evidence of clear superiority over single-agent chemotherapy with chlorambucil and considerably more toxicity.
This agent alkylates and cross-links strands of deoxyribonucleic acid (DNA), inhibiting DNA replication and ribonucleic acid (RNA) transcription. Chlorambucil is an important drug in the treatment of Waldenström macroglobulinemia. It is usually administered when extreme bone marrow infiltration, anemia, splenomegaly, lymphadenopathy, and bleeding are present.
Melphalan inhibits mitosis by cross-linking DNA strands; it ultimately disrupts nucleic acid function.
Cyclophosphamide is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells.
Antimetabolites inhibit cell growth and proliferation. Many combinations of chemotherapeutic agents have been tried, with no evidence of clear superiority over single-agent chemotherapy with chlorambucil and considerably more toxicity.
Cladribine is a synthetic antineoplastic agent for continuous intravenous (IV) infusion. The enzyme deoxycytidine kinase phosphorylates this compound into an active 5+-triphosphate derivative, which, in turn, breaks DNA strands and inhibits DNA synthesis. Cladribine disrupts cell metabolism, causing death to resting and dividing cells.
Fludarabine is a nucleotide analogue of vidarabine converted to 2-fluoro-ara-A, which enters the cell and is phosphorylated to form active metabolite 2-fluoro-ara-adenosine triphosphate (ATP). It inhibits DNA synthesis.
These agents immunomodulate the response to malignant cells.
Doxorubicin inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. The combination of these 2 events can, in turn, inhibit the growth of neoplastic cells. Doxorubicin may be effective in chlorambucil-refractory Waldenström macroglobulinemia.
Antineoplastics, Monoclonal Antibody
These agents immunomodulate the response to malignant cells.
Rituximab is a genetically engineered human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.
Immunomodulators modulate processes that promote immune reactions resulting from diverse stimuli.
This is a protein product manufactured by recombinant DNA technology. It possesses complex antiviral, antineoplastic, and immunomodulating activities.
Interferon gamma-1b is a single-chain polypeptide containing 140 amino acids. It is produced by fermentation of genetically engineered Escherichia coli bacterium containing DNA that encodes for the human protein.
Thalidomide is a derivative of glutethimide. Its mode of action for immunosuppression is unclear. Inhibition of neutrophil chemotaxis and decreased monocyte phagocytosis may occur. Thalidomide may cause a 50-80% reduction of tumor necrosis factor–alpha.
Antineoplastics, Proteasome Inhibitors
Proteosome inhibitors inhibit cell growth and proliferation.
Bortezomib was the first of the anticancer agents known as proteasome inhibitors to be approved. The proteasome pathway is an enzyme complex existing in all cells. This complex degrades ubiquitinated proteins that control the cell cycle and cellular processes and maintains cellular homeostasis. Reversible proteasome inhibition disrupts pathways supporting cell growth, thus decreasing cancer cell survival.
Antineoplastics, mTOr Kinase Inhibitor
These antineoplastic agents have antiproliferative and antiangiogenic properties.
Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that is approved by the US Food and Drug Administration for the treatment of renal cell cancer, subependymal giant cell astrocytoma, and advanced neuroendocrine tumors of pancreatic origin. It is a kinase inhibitor that inhibits antigenic and interleukin (IL-2 and IL-5)–stimulated activation and proliferation of T and B lymphocytes. Phase II studies demonstrate activity in relapsed Waldenström macroglobulinemia.
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