Experimental Drug Treatments for Follicular Lymphoma

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Follicular lymphoma (FL) is the most common form of non-Hodgkin lymphoma.

Non-Hodgkin is one of the main forms of lymphoma, a type of cancer that begins when lymphocytes — white blood cells that are part of the immune system — start multiplying uncontrollably. Follicular lymphoma accounts for about 12 percent of all B-cell non-Hodgkin lymphomas. It grows so slowly that patients often have no symptoms, even at diagnosis.

Common FL symptoms include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, fatigue, shortness of breath, night sweats, and weight loss.

FL usually responds to radiation and chemotherapy. However, many other treatments are being tested for people with FL who have not received previous treatments or who have a relapsed or refractory form of the disease.

Experimental drug treatments for FL

People with FL who have not previously received a treatment have various combinations of therapies available to them. The combinations target specific parts of lymphoma cells, and may work in cases where chemotherapy doesn’t. A lot of clinical trials are recruiting participants to test these treatments. The therapies include:

  • Rituximab, which is already used alone or with other medications to treat certain types of non-Hodgkin’s lymphoma. A Phase 2 clinical trial (NCT02451111) is recruiting patients with advanced FL. It will investigate the safety, effectiveness, and tolerability of a combination of rituximab and ibrutinib. A Phase 3 study (NCT02213263) is recruiting participants who are CD-20-positive and have a low-tumor-burden FL to compare two rituximab treatments — Pfizer’s version vs. Roche’s.
  • Lenalidomide, which is used to treat a variety of bone marrow-related conditions and people with mantle cell lymphoma, a rare type of B-cell non-Hodgkin lymphoma. A Phase 2 trial (NCT02871219) is recruiting participants. It will look at whether a combination of lenalidomide and  obinutuzumab can help control previously untreated FL. Another Phase 2 study (NCT02532257) is assessing whether adding ibrutinib to rituximab and lenalidomide can help control previously untreated FL and marginal zone lymphoma.
  • Bendamustine, which is used to treat chronic lymphocytic leukemia and also to treat a slow-spreading type of non-Hodgkin lymphoma. A Phase 1b/2 study (NCT02596971) by Hoffman-LaRoche will evaluate the safety and effectiveness of atezolizumab as a combo therapy for FL and  diffuse large B-cell lymphoma. FL patients will receive either obinutuzumab plus bendamustine or obinutuzumab plus prednisone. DLBCL patients will receive rituximab plus prednison. The trial is recruiting participants.
  • Crizotinib, which is a tyrosine kinase inhibitor, for lymphomas with ALK protein.
  • Ofatumumab, which is used to treat chronic lymphocytic leukemia, a type of cancer of white blood cells. A Phase 2 study (NCT02710643) will assess the effect of local radiotherapy with and without ofatumumab in stage 1/2 FL. It is recruiting participants.
  • Bortezomib , which is used to treat multiple myeloma.
  • Ibrutinib, which is already used to treat some types of Non-Hodgkin lymphoma. A Phase 3 trial  (NCT02947347) will assess whether adding ibrutinib to rituximab can increase the length of time that the disease fails to progress, compared with rituximab, in FL patients who have yet to receive treatment. It is recruiting participants.
  • Idelalisib, which is also being used to treat some types of Non-Hodgkin lymphoma. A Phase 3 trial (NCT02536300) is aimed at optimizing the safety and effectiveness of administering idelalisib to FL patients. In addition, it will evaluate idelalisib’s safety and patients’ overall response rate by week 24. The yardstick for measuring overall response rate will be the percentage of patients whose tumor size decreases.
  • Phosphatidyl-inositide 3 kinase (PI3K) inhibitors, such as duvelisib and copanlisib, which have shown promise in early studies
  • TGR1202, a PI3K-Delta inhibitor. Two trials testing TGR1202 are recruiting participants. The first one (NCT03178201) is a Phase 2 study to determine relapsed or refractory FL patients’ overall response rate to TGR1202. The second (NCT02793583) is a Phase 2b study assessing the safety and effectiveness of a combination of TG-1101 and TGR-1202, with or without bendamustine, and TGR-1202 alone in participants with previously treated Non-Hodgkin lymphoma.
  • Obinutuzumab, which is used with chlorambucil to treat chronic lymphocytic leukemia. Seventeen clinical trials are recruiting participants.
  • Atezolizumab, for urothelial cancer, or cancer of the lining of the bladder and other parts of the urinary tract. Patients to be tested include those whose urothelial cancer has spread and cannot be removed by surgery, and those who cancer has worsened after treatment with other chemotherapies. A Phase 1b study (NCT02220842) will assess the safety and characteristics of atezolizumab and obinutuzumab in people with relapsed or refractory FL. It will also test a combination of atezolizumab and either obinutuzumab or tazemetostat in people with relapsed or refractory diffuse large B-cell lymphoma. The trial is recruiting participants.
  • Pembrolizumab, which is used to treat several kinds of cancer, including a certain type of Hodgkin lymphoma. The drug will be assessed in children and adults who failed to respond to chemotherapy or whose cancer returned after they were treated three or more times with chemotherapies. A number of studies assessing pembrolizumab alone or in combination are recruiting FL patients.
  • Ruxolitinib, a janus kinase (JAK) inhibitor, which has shown results in early studies.
  • Venetoclax, which has also shown promise in early studies. A Phase 1 trial (NCT02877550) is recruiting participants to assess obinutuzumab in combination with venetoclax in FL patients who have yet to be treated.

Other treatment modalities

Immunochemotherapy, radioimmunotherapy, stem cell transplants, and antibiotics are also being researched as potential treatments for FL.

Immunochemotherapy, also called chemoimmunotherapy, combines two powerful treatment approaches: immunotherapy and chemotherapy. Immunotherapy involves the use of agents that stimulate the immune system to attack and destroy cancer cells. Chemotherapy is the use of drugs designed to destroy or slow the growth of cancer cells.

Radioimmunotherapy, which combines immunotherapy with radiotherapy, can offer advantages in lymphoma treatment because the immunotherapy component is sensitive to radiation in a dose-dependent way. Radioimmunoconjugates recognize and kill lymphoma cells predominantly by radioactive emissions.

Stem cell transplants consist of autologous transplants, which use stem cells from the patient, and non-myeloablative transplants, or cells from donors. Autologous transplants carry a risk of reintroducing lymphoma cells back into a patient after treatment. Better ways to separate the remaining lymphoma cells from the stem cells are being tested. Non-myeloablative stem cell transplants can benefit older people or those whose overall health is poor. That’s because this approach involves using a less aggressive combination of chemotherapy and radiation to prepare a patient for a transplant.

Antibiotics can be used to treat some types of lymphoma that are linked to infections.

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