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.
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Current NHL Research and Clinical Trials
Below are some of the types of NHL research and trials under way:
Drugs Under Study
- The chemotherapy agent bendamustine (Treanda®), approved for chronic lymphocytic leukemia (CLL) and relapsed indolent NHL, is being studied in newly diagnosed mantle cell lymphoma, with rituximab (Rituxan®) and lenalidomide (Revlimid®).
- Bortezomib (Velcade®), a drug called a “proteasome inhibitor” that is approved to treat patients with mantle cell lymphoma who have received at least one prior therapy, is now being investigated for effectiveness as part of initial treatment for mantle cell lymphoma. Researchers are also exploring the use of Velcade in combination with other agents such as Treanda and lenalidomide (Revlimid®).
- Agents called “histone deacetylase (HDAC) inhibitors” are a class of drugs that address “epigenetic” changes in the DNA. One HDAC inhibitor, vorinostat (Zolinza®), which controls how DNA is regulated, is approved for treatment of patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following treatment with two systemic therapies. This agent is now being studied to treat T-cell and B-cell lymphoma both alone and in combination with other drugs.
- The immunomodulatory drug Revlimid is being studied as treatment for diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia (CLL).
- The monoclonal antibody therapy yttrium-90-ibritumomab tiuxetan (Zevalin®) has been approved for relapsed low-grade lymphoma and 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 a monoclonal antibody approved for relapsed CLL and is now being studied in clinical trials in various combinations for the treatment of chronic lymphocytic leukemia, diffuse large B-cell lymphoma and follicular lymphoma.
- Pralatrexate (Foloytn®), approved for various T-cell lymphoma subtypes, is being studied in combination with other chemotherapy drugs. Pralatrexate is a type of chemotherapy 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:
- Everolimus, an mTOR inhibitor, is being studied in combination with other treatments for previously treated NHL.
- Ibrutinib (ImbruvicaTM), a BTK inhibitor that is being studied in previously treated CLL/SLL and mantle cell lymphoma patients.
- Idelalisib, an oral PI3K delta inhibitor, which is being studied for the treatment of patients with indolent NHL that is refractory to Rituxan and to an alkylating agent containing chemotherapy. This drug is being developed as both a single agent and in combination with other therapy.
- Temsirolimus, an mTOR inhibitor, is currently being studied in combination with other treatments for previously treated NHL.
Gene Expression Profiling (GEP) and Tissue Microarrays (TMAs)
These are tools that help us better understand the biology of lymphoma. GEP and TMAs help us characterize lymphoma more carefully. As an example, certain biomarkers in tumor cells are associated with a greater or lesser response to therapy and can serve as predictors indicating whether someone will relapse from therapy or whether their disease will behave either more or less aggressively. Some of the most important of these biomarkers are gene based. A tool used to analyze the activity of genes is called a “microarray.”
There is increasing focus on looking at the tumor microenvironment; that is, the cells that are associated with the tumor, rather than the tumor itself. In follicular lymphoma, certain cells that are actually found next to the tumor cells have been shown to predict a better or worse outcome.
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, transplantation may be an option for patients aged 60 to 70 years. Patients being conditioned for a reduced-intensity 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), 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.
Scientists are developing vaccines that stimulate the immune system to combat and suppress lymphoma cell growth. Unlike classic vaccines, they do not prevent the disease; but if used during remission, they stimulate the immune system to attack the residual lymphoma cells and prevent them from causing a relapse.