Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor updated 5/2021
Treatment for Hodgkin lymphoma is tailored to each individual and may include surgery, radiation therapy, chemotherapy, and use of precision cancer medicines or stem cell transplant in selected situations. The specific treatment depends on the stage of the cancer and its genomic profile.1
Individuals with obvious stage III or IV disease, those with a single large defined mass, mediastinal disease, or the presence of “B” symptoms, are treated with a combination chemotherapy and precision cancer medicines with or without additional radiation therapy.
Individuals with non-bulky stage IA or IIA disease are candidates for chemotherapy, combined chemo-radiation therapy, or radiation therapy alone.1,2
Individuals with recurrent disease are treated with additional chemotherapy and precision cancer medicines, stem cell transplantation, CAR-T cell therapy or on a clinical trial evaluating emerging precision cancer medicines that target Hodgkin lymphoma or a combination of these treatment approaches.1-5
Surgery. The role of surgery in the management of Hodgkin lymphoma is primarily to secure a biopsy specimen for evaluation.
Radiation therapy. Radiation therapy uses high-powered energy beams, such as X-rays or protons, to kill cancer cells. The objective of radiation therapy is to kill cancer cells for a maximum probability of cure with a minimum of side effects. Radiation is usually given in the form of high-energy beams that deposit the radiation dose into the body where cancer cells are located. Radiation therapy, unlike chemotherapy, is considered a local treatment. Cancer cells can only be killed where the actual radiation is delivered to the body. If cancer exists outside the radiation field, the cancer cells are not destroyed by the radiation.
Radiation therapy is an important treatment modality for patients with Hodgkin lymphoma. However, radiation therapy is usually not the sole treatment for Hodgkin lymphoma except in selected circumstances. Chemotherapy alone or combined modality treatment with chemotherapy and radiation therapy is typically utilized even for early stage lymphoma. Therefore, it is essential for patients with Hodgkin lymphoma to be treated at medical centers where medical oncologists, radiation oncologists and surgeons work together.
Systemic Therapy: Precision Cancer Medicine, Chemotherapy, and Immunotherapy
Systemic therapy is any treatment directed at destroying cancer cells throughout the body, and may include chemotherapy or newer precision cancer medicines or immunotherapy. Treatment of patients with stage II, III, IV or recurrent Hodgkin lymphoma often consists of systemic treatment.
Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, administered through a vein, or delivered orally in the form of a pill. Most chemotherapy drugs cannot tell the difference between a cancer cell and a healthy cell. Therefore, chemotherapy often affects the body’s normal tissues and organs, which can result in complications or side effects. In order to more specifically target the cancer and avoid unwanted side effects researchers are increasingly developing precision cancer medicines.
Precision Cancer Medicines
Through genomic-biomarker testing performed on the cancer or in blood doctors are increasingly able to define the genomic alterations in a cancers DNA that is driving the growth of a specific cancer. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Precision medicines have been developed for the treatment of thyroid cancers with identifiable cancer driving mutations.
By testing an individual’s HL for specific unique biomarkers doctors continue to develop new precision medicines. Individuals can undergo genomic testing to determine whether newer precision cancer medicines are a treatment option. These medicines are currently used mainly in the treatment of advanced disease alone or in combination with other therapies.
Adcetris (brentuximab vedotin)
Adcetris is a precision cancer medicine that targets a protein known as CD30, which is present on HL cells. Once Adcetris enters CD30-positive cells, it releases the potent chemotherapy drug monomethyl auristatin E. Adcetris which when combined with chemotherapy has become a standard treatment for the initial treatment of advanced HL.5
Precision immunotherapy treatment of cancer has also progressed considerably over the past few decades and has now become a standard treatment. The immune system is a network of cells, tissues, and biologic substances that defend the body against viruses, bacteria, and cancer. The immune system recognizes cancer cells as foreign and can eliminate them or keep them in check—up to a point. Cancer cells are very good at finding ways to avoid immune destruction, however, so the goal of immunotherapy is to help the immune system eliminate cancer cells by either activating the immune system directly or inhibiting the mechanisms of suppression of the cancer.
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Researchers are mainly focused on two promising types of immunotherapy. One type creates a new, individualized treatment for each patient by removing some of the person’s immune cells, altering them genetically to kill cancer, and then infusing them back into the bloodstream the other uses precision medications to enhance the immune systems response to the cancer.
- Checkpoint Inhibitors: Checkpoint inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the cancer cells. A diagnostic test to measure the level of PD-L1 is available.7,8
- Keytruda (pembrolizumab) is a “checkpoint inhibitor” and has anti-cancer activity in Hodgkin lymphoma. There are several other PD-1 and PD-L1 checkpoint inhibitors being developed.9
High Dose Chemotherapy & Autologous Stem Cell Transplant
High-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) is a standard treatment for the majority of patients with relapsed HL. The basic strategy uses higher doses of chemotherapy and radiation therapy, which kill more cancer cells than lower doses. Unfortunately, the higher doses of therapy used to destroy cancer cells also damages normal cells. The body’s normal cells that are most sensitive to destruction by high-dose therapy are the blood-producing stem cells in the bone marrow. To “rescue” the bone marrow and hasten blood cell production and immune system recovery, high-dose therapy is followed by an infusion of autologous stem cells collected from the patient prior to administering the HDC.10
CAR T-cell Therapy
CAR therapies utilize T-cells (CAR T), a patient’s own immune cells that are re-programmed to recognize and kill cancer cells throughout the body. In essence, CAR T cell therapy is a type of gene therapy that modifies a patient’s own T cells (a type of immune cell) to detect and kill the patient’s cancer cells.
The process involves the removal of some T cells from a patient, and through laboratory processes, these T cells are re-programmed to identify a patient’s cancer cells. It is unique in comparison to other types of available immune therapies for cancer, in that the patient’s own T cells are the actual treatment; no other medications are used as an active component of therapy.
Treatment of Hodgkin Lymphoma by Stage
Stage I: Cancer is found only in a single lymph node, in the area immediately surrounding that node or in a single organ.
Stage II: Cancer involves more than one lymph node on one side of the diaphragm (the breathing muscle separating the abdomen from the chest).
Stage III: The cancer involves lymph node regions above and below the diaphragm. For example, there may be swollen lymph nodes under the arm and in the abdomen.
Stage IV: Cancer involves one or more organs outside the lymph system or a single organ and a distant lymph node site.
Patients with Hodgkin lymphoma may also experience general symptoms from their lymphoma. Patients with fever, night sweats or significant weight loss are said to have “B” symptoms. Patients who do not experience these specific symptoms are classified as “A”.
Relapsed/Refractory: The cancer has persisted or returned (recurred/relapsed) following treatment.
- Armitage JO: Early-stage Hodgkin’s lymphoma. N Engl J Med 363 (7): 653-62, 2010.
- Advani RH, Horning SJ: Treatment of early-stage Hodgkin’s disease. Semin Hematol 36 (3): 270-81, 1999.
- Nademanee A, O’Donnell MR, Snyder DS, et al.: High-dose chemotherapy with or without total body irradiation followed by autologous bone marrow and/or peripheral blood stem cell transplantation for patients with relapsed and refractory Hodgkin’s disease: results in 85 patients with analysis of prognostic factors. Blood 85 (5): 1381-90, 1995.
- Gopal AK, Ramchandren R, O’Connor OA, et al.: Safety and efficacy of brentuximab vedotin for Hodgkin lymphoma recurring after allogeneic stem cell transplantation. Blood 120 (3): 560-8, 2012.
- Younes A, Bartlett NL, Leonard JP, et al.: Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 363 (19): 1812-21, 2010.
- Moskowitz C, Nadamanee A, Masszi T, et al. The Aethera Trial: Results of a Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Brentuximab Vedotin in the Treatment of Patients at Risk of Progression Following Autologous Stem Cell Transplant for Hodgkin Lymphoma. Presented at the 56th Annual Meeting of the American Society of Hematology, December 6-9, 2014. Abstract 673.
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- Moskowitz C, Ribrag V, Michot J-M, et al. PD-1 Blockade with the Monoclonal Antibody Pembrolizumab (MK-3475) in Patients with Classical Hodgkin Lymphoma after Brentuximab Vedotin Failure: Preliminary Results from a Phase 1b Study (KEYNOTE-013). Presented at the 56th Annual Meeting of the American Society of Hematology. December 6-9, 2014. Abstract 290.
- Sirohi B, Cunningham D, Powles R, et al. Long-term outcome of autologous stem-cell transplantation in relapsed or refractory Hodgkin’s lymphoma. Annals of Oncology. 2008;19:1312-1319.