Taking part in a clinical trial may be the best treatment choice for some non-Hodgkin lymphoma (NHL) patients. Clinical trials are under way to develop treatments that increase the remission rate of 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 NHL research.
Click here to read more about clinical trials.
Current NHL Research and Clinical Trials
Below are some of the types of NHL research and trials under way:
Drugs Under Study
- Agents called “histone deacetylase (HDAC) inhibitors” are a class of drugs that address “epigenetic” changes in the DNA. Examples include vorinostat (Zolinza®), romidepsin (Istodax®) and belinostat (Beleodaq®), among others.
- The immunomodulatory drug lenalidomide (Revlimid®) is being studied as a single agent and in combination with other drugs for the treatment of diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia (CLL).
- Pralatrexate (Foloytn®), approved for various T-cell lymphoma subtypes, is being studied as a single agent and in combination with other chemotherapy drugs for treating various relapsed and refractory B-cell and T-cell NHLs. Pralatrexate is an antifolate drug that disrupts processes in cells that are required for cell replication.
- There are several other drugs under investigation that target B-cell receptor signaling pathways inside the lymphoma cells. Some of these drugs include
- Ibrutinib (Imbruvica®), a BTK inhibitor that is approved for treating Waldenström macroglobulinemia and previously-treated mantle cell lymphoma (MCL). It is now being studied in combination with other drugs to treat various indolent and aggressive NHLs.
- The PI3K inhibitor idelalisib (Zydelig®), approved for the treatment of patients with relapsed CLL/SLL, is being studied in combination with other agents for relapsed or refractory indolent B-cell NHL and MCL.
- Immunotherapy with monoclonal antibodies
- Brentuximab vedotin (Adcetris®) targets CD30 and is used for treating peripheral T cell lymphomas and Hodgkin lymphomas. It is under study in clinical trials for treating systemic anaplastic large cell lymphoma and other previously treated NHLs.
- Yttrium-90+ibritumomab tiuxetan (Zevalin®) has been approved for previously untreated follicular NHL patients who achieve a partial or complete response to first-line chemotherapy. The effectiveness of this agent is now being studied in the retreatment of lymphoma, as therapy for newly diagnosed indolent lymphoma, as therapy for aggressive forms of NHL in combination with or following other drug regimens, and as part of high-dose therapy programs along with autologous stem cell transplantation.
- Ofatumumab (Arzerra®) is an anti-CD20 antibody approved for relapsed CLL. It is now being studied in clinical trials in various combinations for the treatment of Waldenström macroglobulinemia, DLBCL and follicular lymphoma.
- Obinutuzumab (Gazyva®) is an antibody that targets CD20. It is being used in the treatment of some types of NHLs including refractory follicular lymphoma. It is currently being studied in clinical trials (in combination with other agents) for treating relapsed and refractory CLL/SLL.
Reduced-Intensity Stem Cell Transplantation (Nonmyeloablative Allogeneic Transplantation)
Clinical trials are under way to determine the usefulness of this approach in older and sicker patients for many blood cancers, including some NHL subtypes. As a result, stem cell transplantation may be an option for patients aged 60 to 70 years and older. Patients being conditioned for a reducedintensity transplant receive lower doses of chemotherapy drugs and/or radiation in preparation for the transplant. Immunosuppressive drugs are used to prevent rejection of the graft (the donor immune cells), thereby allowing the engrafted immune cells to attack the recipient’s disease. The effectiveness of reduced-intensity transplantation is due to the graft-versus-lymphoma effect of the donor’s lymphocytes rather than to high doses of chemotherapy.
CAR T-Cell Therapy
This is a type of immunotherapy that consists of engineering a patient’s own immune cells to recognize and then attack cancerous tumors. This approach has shown very promising results in patients with blood cancers. The patient’s T cells are genetically engineered to produce receptors on their surface called “chimeric antigen receptors (CARs).” These receptors recognize and bind to a specific target found on the cancer cells. In an ongoing clinical trial, researchers are studying the role of CAR T-cell therapy in patients with relapsed or refractory aggressive B-cell NHL.
For more information on this type of therapy, please see the LLS fact sheet Chimeric Antigen Receptor (CAR) T-Cell Therapy Facts.
PD-1 Checkpoint Inhibitors
A vital part of the immune system is its ability to tell the difference between healthy cells in the body from those that are foreign or harmful. The immune system depends on multiple “checkpoints,” in which molecules on certain immune cells need to be activated or inactivated in order to start an immune response. Cancer cells sometimes take advantage of these checkpoints to escape the detection of active immune cells.
Programmed cell death 1 (PD-1) is a checkpoint protein that is found on the surface of T cells. It normally acts as a type of “off switch” that helps prevent immune cells from attacking healthy cells in the body. It accomplishes this when it attaches to PD-L1, a protein found on some normal cells and also in some cancer cells. When PD1 binds to PD-L1, a message is sent to the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1 receptors, which help them avoid an immune attack.
Checkpoint inhibitors are drugs created to target the PD1 or PD-L1, blocking their actions, and allowing the immune system to recognize and eliminate cancer cells. One example of this type of drug is nivolumab (Opdivo®), which has shown positive results in other cancers such as melanoma and is now being studied as a single agent and in combination with other drugs for the treatment of B-cell and T-cell non-Hodgkin lymphomas. Another checkpoint inhibitor drug is pidilizumab, which is now being studied in trials for the treatment of relapsed follicular lymphoma.