Taking part in a clinical trial may be the best treatment choice for some Hodgkin lymphoma (HL) patients. Clinical trials are under way to develop treatments that increase the remission rate or cure the disease. Today's standard treatments for cancer are based on earlier clinical trials. The Leukemia & Lymphoma Society continues to invest funds in HL research.
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Current Hodgkin Lymphoma Research and Clinical Trials
There are clinical trials for both newly diagnosed patients and patients with relapsed or refractory disease. A number of approaches are under study in clinical trials for the treatment of patients with HL.
Genetic Studies. HL is a rare disease. Nonetheless, it may affect more than one person in the same family. This supports the theory that there is a genetic basis for HL risk. Studies of familial HL are under way to obtain a better understanding of the genetic causes of the disease and to determine which genetic variations are responsible for recurring HL in families. This information may help doctors predict a person’s risk of developing HL, and also help scientists discover biological pathways that can be targeted with novel treatments.
Interim Positron Emission Tomography-Computed Tomography (PET-CT) as a Decision Tool for Risk-Adapted Therapy. Recent studies have focused on assessing the role of interim and “restaging” PET-CT scans in patients with Hodgkin lymphoma. Accurate mid-treatment restaging is expected to enable tailoring of treatment, allowing healthcare professionals to improve remission rates while minimizing toxicities. Some of these studies are comparing different chemotherapy regimens (such as ABVD and BEACOPP) in both advanced- and early-stage disease. At the same time, PET-CT is used to help doctors to determine which patients will benefit most from more intensive treatment versus treatment de-escalation
Monoclonal Antibodies. Monoclonal antibodies are immunotherapy drugs especially designed to target specific proteins (antigens) in cancer cells. Once the antibody finds and attaches to its target cell, it can recruit other parts of the immune system to destroy the cell that contains the antigen. Some monoclonal antibodies are coupled with a chemotherapy drug or attached to a radioactive particle. They circulate throughout the body until they attach to a target antigen and then deliver the toxic substance to the cancer cell. Brentuximab vedotin (Adcetris®), which targets CD30 (cluster of differentiation 30) and releases a chemotherapy drug into the cell causing its death, is FDA-approved for treatment of relapsed or refractory HL after failure of an autologous stem cell transplant. Various clinical trials are studying the use of this agent
- In combination with standard chemotherapy (AVD: Adriamycin [doxorubicin], vinblastine, dacarbazine as initial treatment for advanced HL [bleomycin was omitted in order to avoid pulmonary toxicity])
- As a consolidation treatment option to be administered after an autologous stem cell transplant
Programmed Death (PD-1) Checkpoint Inhibitors. A vital part of the immune system is its ability to distinguish between healthy cells in the body and those that are foreign or harmful. The immune system depends on multiple programmed death (PD-1 checkpoints). Checkpoints are molecules on certain immune cells that need to be activated (or turned off) in order to start an immune response. Cancer cells sometimes take advantage of these checkpoints to escape the detection of active immune cells. A checkpoint protein, PD-1 is found on the surface of T cells. It normally acts as a type of “off switch” that helps keep immune cells from attacking healthy cells in the body. It accomplishes this when it attaches to a PDL1, a protein found on some other normal cells, as well as in some cancer cells. When PD-1 binds to PD-L1, a message is sent to the T cell to leave the other cell alone and not attack it. But some cancer cells also have large amounts of PD-L1 receptors, which help them avoid a normal immune attack. Checkpoint inhibitors are monoclonal antibodies created to target PD-1 or PD-L1, blocking their actions, and allowing the immune system to recognize and eliminate cancer cells. Two checkpoint inhibitor drugs nivolumab (Opdivo®) and pembrolizumab (Keytruda®), both now approved for refractory and relapsed cHL, are being studied with various other agents.
Standard Chemotherapy vs Combined Modality Treatment. There is considerable interest in studying the use of chemotherapy alone (without radiation therapy) for the treatment of patients with early-stage HL. Several studies suggest that this may be a very reasonable approach for many patients. Studies in this area include
- Comparing outcomes between the use of chemotherapy alone and the use of combined modality therapy (chemotherapy with involved-field radiation therapy [IFRT])
- Collecting and analyzing data on the long-term side effects of ABVD and involved-field radiation therapy IFRT
- Comparing outcomes between the uses of involved-field radiation therapy (IFRT) and involved-site radiation therapy (ISRT) or involved-node radiation therapy (INRT), which target smaller areas for radiation.