Medication Summary
The monoclonal antibody rituximab, as monotherapy or in combination with the alkylating agent bendamustine or a proteosome inhibitor, features prominently in treatment of Waldenström macroglobulinemia. Other drugs used include alkylating agents, purine nucleoside analogs, immunomodulatory drugs, mammalian target of rapamycin (mTOR) inhibitors, and tyrosine kinase inhibitors (TKIs).
Salvage therapy for patients with resistant disease or relapse includes reuse or alternative use of front-line agents, combination therapy, thalidomide (with or without steroids), autologous transplantation, and monoclonal antibody (alemtuzumab).
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.
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 indicated for Waldenström macroglobulinemia as either a single-agent or in combination with rituximab.
Zanubrutinib (Brukinsa)
Zanubrutinib 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 and cytokine receptor pathways. BTK's role in signaling through the B-cell surface receptors results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. It is indicated for Waldenström macroglobulinemia as a single agent.
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.
Bendamustine (Bendeka)
Alkylating agent that cross-links single or double DNA strands resulting in DNA breakdown; cell cycle-nonspecific
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.
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.
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.
Immunomodulators
Class Summary
Immunomodulators modulate processes that promote immune reactions resulting from diverse stimuli.
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.
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.
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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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.
Tables
Point total |
Risk group |
3-year WM-related death rate (%) |
10-year overall survival rate (%) |
| 0 | Very low |
0 |
84 |
| 1 | Low | 10 |
59 |
| 2 | Intermediate | 14 |
37 |
| 3 | High | 38 |
19 |
| 4-5 | Very high |
48 |
9 |
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Guidelines
- Medication
- Medication Summary
- Corticosteroids
- Antineoplastics, Tyrosine Kinase Inhibitor
- Antineoplastics, Alkylating
- Antineoplastics, Antimetabolite
- Antineoplastics, Anthracycline
- Antineoplastics, Monoclonal Antibody
- Immunomodulators
- Antineoplastics, Proteasome Inhibitors
- Antineoplastics, mTOr Kinase Inhibitor
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