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Waldenstrom Macroglobulinemia Medication

  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
 
Updated: Jan 15, 2016
 

Medication Summary

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).

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Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone

 

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.

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Antineoplastics, Tyrosine Kinase Inhibitor

Class Summary

Tyrosine kinase enzymes are responsible for activating many proteins by signal transduction cascades, phosphorylation, and other mechanisms. Tyrosine kinase inhibitors block these functions.

Ibrutinib (Imbruvica)

 

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.

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Antineoplastics, Alkylating

Class Summary

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.

Chlorambucil (Leukeran)

 

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 (Alkeran)

 

Melphalan inhibits mitosis by cross-linking DNA strands; it ultimately disrupts nucleic acid function.

Cyclophosphamide

 

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.

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Antineoplastics, Antimetabolite

Class Summary

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 (Leustatin)

 

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 (Fludara)

 

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.

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Antineoplastics, Anthracycline

Class Summary

These agents immunomodulate the response to malignant cells.

Doxorubicin (Adriamycin)

 

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.

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Antineoplastics, Monoclonal Antibody

Class Summary

These agents immunomodulate the response to malignant cells.

Rituximab (Rituxan)

 

Rituximab is a genetically engineered human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes.

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Immunomodulators

Class Summary

Immunomodulators modulate processes that promote immune reactions resulting from diverse stimuli.

Interferon alfa-2b (Intron A)

 

This is a protein product manufactured by recombinant DNA technology. It possesses complex antiviral, antineoplastic, and immunomodulating activities.

Interferon gamma-1b (Actimmune)

 

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 (Thalomid)

 

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.

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Antineoplastics, Proteasome Inhibitors

Class Summary

Proteosome inhibitors inhibit cell growth and proliferation.

Bortezomib (Velcade)

 

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.

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Antineoplastics, mTOr Kinase Inhibitor

Class Summary

These antineoplastic agents have antiproliferative and antiangiogenic properties.

Everolimus (Afinitor, Zortress)

 

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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Contributor Information and Disclosures
Author

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.

Coauthor(s)

Doris Ponce, MD Fellow, Department of Hematology/Oncology, New York Medical College

Doris Ponce, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Hematology, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Wendy Hu, MD Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center

Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

Vijay Ramu, MBBS Staff Physician, Department of Internal Medicine, East Tennessee State University

Vijay Ramu, MBBS is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Harsha Vyas, MD Fellow, Section of Hematology and Oncology, Wake Forest University School of Medicine

Harsha Vyas, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, and American Society of Hematology

Disclosure: Nothing to disclose.

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Purpura from Waldenström macroglobulinemia is evident in the forearm of a 65-year-old man who presented with a purpuric rash on all of his extremities. Although the patient had a history of hepatitis C, the possibility of hepatitis C cryoglobulinemia was excluded because the rash extended well beyond the hands and feet, and blood testing identified a type I cryoglobulinemia. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.
 
 
 
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