Medication Summary
Several chemotherapeutic agents in various combinations are used to treat Hodgkin lymphoma. The combinations vary by the stage of disease and by the treating institution. In patients with relapsing or unresponsive disease, hematopoietic stem-cell transplantation significantly prolongs disease-free survival. Various drug combinations have been used with stem-cell rescue.
Although the intended target is the malignant cells of Hodgkin lymphoma, the effects of chemotherapy on normal cells of the body are considerable and account for the adverse effects observed with these agents. Because most patients with Hodgkin lymphoma are long-term survivors, one of the goals of current therapy is to decrease the long-term adverse effects while maintaining excellent cure rates. The use of different therapeutic agents with nonoverlapping toxicities is one way to achieve this goal. Various combinations of the drugs presented below are used to treat Hodgkin lymphoma .
Although adverse effects vary with each drug, some are common to many drugs. These adverse effects include nausea, vomiting, alopecia, bone marrow suppression, and, less commonly, secondary malignancies.
Cancer chemotherapy is based on an understanding of tumor cell growth and of how drugs affect this growth. After cells divide, they enter a period of growth (ie, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2), then finally a mitotic cell division (ie, phase M).
Cell-division rates vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the growth rate may be decreased in large tumors. This difference allows normal cells to recover more quickly than malignant ones after chemotherapy and is the rationale behind current cyclic dosage schedules.
Antineoplastics, Alkylating
Class Summary
Antineoplastic agents interfere with cell reproduction. Some agents are specific to phases of the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.
Alkylating antineoplastic agents elicit their effects through the formation of covalent bonds with DNA, which disturbs protein synthesis and cellular division. They are able to form bonds with DNA of all cells, especially those which reproduce rapidly. Because of their nonspecific action on cells, toxicities to normal cells are an issue.
Mechlorethamine (Mustargen)
Mechloroethamine is a component of the MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen. It exerts cytotoxic effect by inhibiting rapid proliferation of cancer cells.
Antineoplastics, Antibiotic
Class Summary
Antibiotic antineoplastic agents are produced by microorganisms and inhibit or prevent the proliferation of neoplasms.
Bleomycin (Blenoxane)
Classified as an antibiotic, bleomycin induces free radical-mediated breaks in strands of DNA. This agent is part of the ABVD (Adriamycin [doxorubicin], bleomycin, vinblastine, dacarbazine) regimen.
Antineoplastics, Vinca Alkaloid
Class Summary
The vinca alkaloid agents are naturally occurring or semisynthetic nitrogenous bases that elicit their cytotoxic effects through tubulin-binding properties and disruption of microtubule function, which lead to metaphase arrest.
Vinblastine (Velban)
Vinblastine is a vinca alkaloid that inhibits mitosis because of interactions with tubulin.
Dacarbazine (DTIC-Dome)
Dacarbazine is an alkylating agent that inhibits DNA, RNA, and protein synthesis. It inhibits cell replication in all phases of the cell cycle.
Vincristine (Vincasar PFS, Oncovin)
Vincristine is a vinca alkaloid with a mechanism of action similar to that of vinblastine. It is presumed to stop the metaphase stage therefore preventing microtubule formation in the mitotic spindle.
Antineoplastics, Podophyllotoxin Derivatives
Class Summary
Podophyllotoxin derivative antineoplastic agents have cytotoxic effects on cell growth.
Etoposide (Toposar)
Etoposide is an epipodophyllotoxin that induces DNA strand breaks by disrupting topoisomerase II activity. This causes cell proliferation to arrest in the late S or early G2 portion of the cell cycle.
Procarbazine (Matulane)
Procarbazine is an alkylating agent with a mechanism of action similar to that of dacarbazine: inhibition of DNA, RNA, and protein synthesis. It inhibits cell replication in all phases of the cell cycle. It is part of COPP, BEACOPP and MOPP regimens.
Antineoplastics, Alkylating, DMARDs, Immunomodulators
Class Summary
Cyclophosphamide is a synthetic agent similar to nitrogen mustard. This agent requires activation in the liver to form its active intermediaries, which in turn modify and cross-link DNA, thereby inhibiting DNA, RNA, and protein synthesis. Eventually, apoptosis occurs.
Cyclophosphamide (Cytoxan)
Cyclophosphamide is an alkylating agent that is chemically related to nitrogen mustards. The mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Immunosuppressants; Antineoplastics, Antimetabolite; DMARDs, Immunomodulators
Class Summary
Antimetabolite antineoplastic agents interfere with cell functions by competing for its receptors or enzymes involved in the synthesis of DNA. Tissues that have a high rate of cellular metabolism are most sensitive to the effects.
Methotrexate (Rheumatrex, Trexall)
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, which is necessary for conversion of folate to biologically active tetrahydrofolate.
Antineoplastics, Anthracyclines
Class Summary
Anthracycline antineoplastic agents elicit their cytotoxic effects through nucleotide base intercalation and cell membrane lipid-binding. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases.
Doxorubicin (Adriamycin)
An anthracycline that functions as a DNA intercalator, doxorubicin inhibits topoisomerase II and produces free radicals, which may destroy DNA. The combination of these 2 events can inhibit the growth of neoplastic cells. Doxorubicin is administered intravenously and distributes widely into bodily tissues, including the heart, kidneys, lungs, liver, and spleen. It does not cross the blood-brain barrier and is excreted primarily in bile.
Antineoplastics, Antimicrotubular
Class Summary
Antimicrotubular antineoplastics disrupt the microtubular network in cells by promoting stabilization and assembly. In addition, these agents block the disassembly of microtubules, thereby preventing cell division, leading to cell death.
Brentuximab vedotin (Adcetris)
Brentuximab is a CD30-directed antibody-drug conjugate (ADC) that consists of chimeric IgG1 antibody cAC10, which is specific for human CD30, bound to the microtubule-disrupting agent monomethyl auristatin E (MMAE, or vedotin). This agent is indicated for treatment of classic Hodgkin lymphoma (cHL) after failure of autologous stem cell transplant (ASCT) or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. It is also indicated as consolidation treatment post-auto-HSCT in patients with high risk for relapse or disease progression. Additionally, brentuximab vedotin is indicated as first-line therapy for previously untreated stage III-IV cHL in combination with chemotherapy.
PD-1/PD-L1 Inhibitors
Class Summary
Immunotherapy is emerging for use in hematologic malignancies.
PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions. PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound.
This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation.
Nivolumab (Opdivo)
Monoclonal antibody which inhibits suppression of T-cells by blocking the interaction between programmed cell death-1 protein and its ligands. Nivolumab is indicated for the treatment of classical Hodgkin lymphoma in patients who have relapsed or shown progression after autologous hematopoietic stem cell transplantation (HSCT) and post transplantation brentuximab vedotin.
Pembrolizumab (Keytruda)
Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. It is indicated for adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL) or who have relapsed after 3 or more prior lines of therapy.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.
Prednisone (Deltasone)
Prednisone is a corticosteroid used to treat leukemias and lymphomas because of its lympholytic activity. Prednisone acts as an immunosuppressant by stimulating the synthesis of enzymes needed to decrease the inflammatory response. It also acts as an anti-inflammatory agent by inhibiting the recruitment of leukocytes and monocyte-macrophages into affected areas via inhibition of chemotactic factors and factors that increase capillary permeability.
Prednisone is readily absorbed via the gastrointestinal tract and metabolized in the liver. Inactive metabolites are excreted via the kidneys. Most of the adverse effects of corticosteroids are dose dependent or duration dependent.
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Micrograph of Hodgkin lymphoma in a fine-needle aspiration lymph node specimen (field stain). Eosinophils, Reed-Sternberg cells, plasma cells, and histocytes can be seen.
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Nodular sclerosing Hodgkin lymphoma of the mediastinum. The diagnosis is strongly suggested by the presence of distinct nodules on the cut surface of this lymph node.
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A Reed-Sternberg cell in Hodgkin lymphoma. Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. Image courtesy of National Cancer Institute.
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Mixed cellularity Hodgkin lymphoma showing both mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells (hematoxylin and eosin, original magnification x200).
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Very high magnification micrograph of nodular lymphoctye predominant Hodgkin lymphoma (NLPHL), with a popcorn-shaped Reed-Sternberg cell (hematoxylin and eosin).
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A positron emission tomography (PET) scan obtained with fluorodeoxyglucose (FDG) that shows increased FDG uptake in a mediastinal lymph node.
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A computed tomography (CT) scan showing bulk disease in a patient with Hodgkin lymphoma.
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This computed tomography scan is from a 46-year patient with Hodgkin lymphoma at the level of the neck. Enlarged lymph nodes are visible on the left side of the neck (red-shaded region).
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This image depicts a computed tomography (CT) scan, positron-emission tomography (PET) scan, and maximum intensity projection (MIP) PET scan from a patient with histologically proven Hodgkin lymphoma.
Tables
- Table 1. Stage Distribution and 5-Year Relative Survival by Stage at Diagnosis for All Races and Both Sexes: 2011-2015
- Table 1. Cotswold Modification of Ann Arbor Staging System
- Table 2. International Conference on Malignant Lymphomas Modification of Ann Arbor Staging
- Table 3. Unfavorable Risk Factors for Stages I and II Hodgkin Lymphoma
Stage at Diagnosis |
Stage Distribution, % |
5-year Relative Survival, % |
Stage I (only in originating layer of cells) |
15 |
92.3 |
Stage II (confined to primary site) |
40 |
93.4 |
Stage III (spread to regional lymph nodes) |
21 |
83.0 |
Stage IV (cancer has metastasized) |
20 |
72.9 |
Unstaged |
4 |
82.7 |
Source: National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at: http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: September 12, 2018 |
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Stage |
Area of Involvement |
I |
Single lymph node group |
II |
Multiple lymph node groups on same side of diaphragm |
III |
Multiple lymph node groups on both sides of diaphragm |
Stage |
Area of Involvement |
Extranodal (E) Status |
|
I |
Single node or adjacent group of nodes |
Single extranodal lesions without nodal involvement |
|
II |
Multiple lymph node groups on same side of diaphragm |
Stage I or II by nodal extent with limited contiguous extranodal involvement |
|
II bulky* |
Multiple lymph node groups on same side of diaphragm with bulk >10 cm |
N/A |
|
III |
Multiple lymph node groups on both sides of diaphragm; nodes above the diaphragm with spleen involvement |
N/A |
|
IV |
Multiple noncontiguous extranodal sites |
N/A |
|
A/B |
B symptoms: weight loss >10%, fever, drenching night sweats |
N/A |
|
*Stage II bulky disease is defined as limited or advanced on the basis of histology and a number of prognostic factors. |
|||
Risk Factor |
GSHG |
EORTC/LSA |
|
Age |
– |
≥50 y |
|
Histology |
– |
MC or LD |
|
ESR or B symptoms |
>50 mm/hr if A or >30 if B |
>50 mm/hr if A or > 30 if B |
|
Mediastinal mass* |
MMR >0.33 |
MMR >0.35 |
|
Number of nodal sites |
>2 |
>3 |
|
Extranodal lesions |
Any |
– |
|
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is the maximum width of the mass/maximum intrathoracic diameter.ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity. |
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- Overview
- Presentation
- DDx
- Workup
- Treatment
- Approach Considerations
- Goals of Therapy and Response Assessment
- Radiation Therapy
- Induction Chemotherapy Regimens
- Salvage Chemotherapy Regimens
- Hematopoietic Stem Cell Transplantation
- Treatment of Early-Stage, Low-Risk Disease
- Treatment of Early-Stage Disease with Unfavorable Factors
- Treatment of Advanced Disease
- Treatment of Nodular Lymphocyte-Predominant Hodgkin Lymphoma
- Treatment in HIV-Infected Patients
- Treatment of Refractory or Relapsed Disease
- Complications of Therapy
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- Medication
- Medication Summary
- Antineoplastics, Alkylating
- Antineoplastics, Antibiotic
- Antineoplastics, Vinca Alkaloid
- Antineoplastics, Podophyllotoxin Derivatives
- Antineoplastics, Alkylating, DMARDs, Immunomodulators
- Immunosuppressants; Antineoplastics, Antimetabolite; DMARDs, Immunomodulators
- Antineoplastics, Anthracyclines
- Antineoplastics, Antimicrotubular
- PD-1/PD-L1 Inhibitors
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