Treatment & Management

of Hodgkin Lymphoma

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 combination chemotherapy 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, stem cell transplantation, on a clinical trial, emerging precision cancer medicines that target Hodgkin lymphoma or a combination of these treatment approaches.1,2,34,5

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.

Learn more about radiation therapy for NL.

Chemotherapy. Chemotherapy uses drugs to kill cancer cells and is a key component in the treatment of Hodgkin lymphoma. A single drug or a combination of drugs may be used.  Chemotherapy can be combined with radiation therapy in some situations, since chemotherapy may enhance the effects of the radiation.  Chemotherapy drugs may be given intravenously (through a vein that carries the drugs throughout the body). The drugs are usually given in cycles so that a recovery period follows every treatment period.

Precision Cancer Medicines

The purpose of precision cancer medicine is define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. 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.

By testing an individual’s Hodgkin lymphoma 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.

Because of CD30 expression on malignant Reed-Sternberg cells of Hodgkin lymphoma, but limited expression on normal cells, CD30 is a target for therapy. Adcetris® (brentuximab vedotin) is a chimeric antibody directed against CD30, which is linked to microtubule-disrupting agent.4,5

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.6,7

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 developed8

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.

Next: Radiation Therapy for Hodgkin lymphoma

Next: Understanding Stem Cell Transplant

References

1 Armitage JO: Early-stage Hodgkin’s lymphoma. N Engl J Med 363 (7): 653-62, 2010.

2 Advani RH, Horning SJ: Treatment of early-stage Hodgkin’s disease. Semin Hematol 36 (3): 270-81, 1999.

3 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.

4 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.

5 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.

6 https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm560167.htm

7 https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm569366.htm

8 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.