Taking part in a clinical trial may be the best therapy 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. Clinical trials are carefully designed and reviewed by expert clinicians and researchers to ensure safety and scientific accuracy. The Leukemia & Lymphoma Society continues to invest funds in NHL research.
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Current NHL Research and Clinical Trials
A number of approaches are under study in clinical trials for the treatment of patients with NHL. The following specific examples are some of the treatment approaches and drugs under study:
- Ofatumumab (Arzerra®)—an anticluster of differentiation 20 (anti-CD20) antibody that is approved by the Food and Drug Administration (FDA) for the treatment of relapsed chronic lymphocytic leukemia (CLL). It is being evaluated (administered in various combinations with other medications) for the treatment of mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).
- Obinutuzumab (Gazyva®)—an anti-CD20 antibody already approved by the FDA for CLL treatment. It is currently under study for the treatment of refractory FL, relapsed and refractory CLL, small-cell lymphocytic leukemia (SLL) and indolent lymphomas that do not respond to rituximab.
- Blinatumomab (Blincyto®)—a bispecific antibody that targets CD19 and CD3. It is under investigation for previously treated DLBCL and indolent lymphoma patients.
- Mogamulizumab (Poteligeo®)—an antibody targeting chemokine receptor 4 (CCR4) that is FDA approved for the treatment of relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after prior therapy. It is now in clinical trials for various subtypes of NHL, including relapsed or refractory cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL) and DLBCL.
- Nivolumab (Opdivo®)—an antiprogrammed death-1 (anti-PD-1) antibody currently being studied for the treatment of relapsed or refractory central nervous system (CNS) lymphoma, FL and DLBCL.
- Pembrolizumab (Keytruda®)—already FDA approved for the treatment of refractory or relapsed primary mediastinal large B-cell lymphoma (PMBCL), and now under study for the treatment of DLBCL, PMBCL, FL and other lymphomas.
- Polatuzumab vedotin-piiq (Polivy™)—an antibody-drug conjugate targeting CD79b that is FDA approved for the treatment of relapsed and refractory DLBCL. Current trials are exploring its use in combination with other targeted therapies for several types of NHL.
- Phosphoinositide 3-kinase (PI3K) inhibitor
- Idelalisib (Zydelig®)—FDA approved for the treatment of chronic lymphocytic leukemia and refractory indolent NHL. This agent is being explored in combination with chemotherapy and other drugs for the treatment of relapsed or refractory indolent B-cell NHL, mantle cell lymphoma (MCL) and marginal zone lymphoma.
- Umbralisib (TGR-1202)—an oral, once daily, dual inhibitor of PI3K delta and CK1 epsilon is being studied in patients with CLL and NHL.
- Bruton Tyrosine Kinase (BTK) Inhibitor
- Ibrutinib (Imbruvica®)—a BTK inhibitor already approved by the FDA for the treatment of several types of NHL. It is being evaluated for the treatment of patients with relapsed and refractory, non-GCB subtypes of DLBCL who are not candidates for autologous stem cell transplantation.
- mTOR Inhibitor
- Temsirolimus (Torisel®)—an inhibitor that blocks a protein involved in cell division. It is currently under study for relapsed and refractory DLBCL.
- Other Agents
- The oral selective inhibitor of nuclear export (SINE), selinexor (KPT-330)— an inhibitor that is currently being evaluated for the treatment of DLBCL. This drug acts by blocking the transport of nuclear proteins in malignant cells, leading to cell death.
- CPI-613® (devimistat)—an antimitochondrial metabolism agent that blocks the mitochondrial cycle used by cancer cells to survive and multiply. It is being evaluated in trials for treating refractory or relapsed Burkitt lymphoma.
- Tazemetostat---a first-in-class small molecule EZH2 inhibitor given by mouth, is currently in clinical trials for relapsed/refractory non-Hodgkin lymphoma.
- Chimeric antigen receptor (CAR) T-cell therapy—a type of immunotherapy that consists of engineering a patient’s own immune cells to recognize and then attack cancerous tumor cells. Axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®) are FDA approved for the treatment of relapsed and refractory DLBCL. Several ongoing studies of CAR T-cell therapy targeting CD19 are evaluating the effectiveness of this therapy for treating refractory and relapsed NHL. For more information on CAR T-cell therapy, see the free LLS booklet Chimeric Antigen Receptor (CAR) T-Cell Therapy.
- Reduced-Intensity Stem Cell Transplantation (Nonmyeloablative Allogeneic Transplantation)—a type of transplantation that is a potential option for older and sicker patients. Studies are under way to evaluate and determine its effectiveness as treatment for many blood cancers, including some NHL subtypes. Patients undergoing a reduced-intensity transplant receive lower doses of chemotherapy drugs and/or radiation therapy in preparation for the transplant. 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
For information about some of the drugs listed on this page, visit Drug Listings.