Relapsed/Refractory Follicular Lymphoma Treatment

The treatment of relapsed or refractory follicular lymphoma (RRFL) is distinct from patients who are receiving treatment for the first time, due to differences in the nature of the disease.

Relapsed and refractory follicular lymphomas are associated with a low likelihood of success using standard treatment options. As a result, they require an alternative plan for responsive therapy in order to achieve favorable outcomes.

Aim of Treatment

The aim of treatment of relapsed/refractory follicular lymphoma is to prolong life with the minimum impact of side effects possible. With adequate treatment, patients may survive for many years. According to current research, approximately 1 in 4 patients who respond to the first secondary treatment survive for 3-5 years. In general, the higher the number of re-treatments, the shorter the cases of remission will be and the lower the survival rate.

Treatment Approach

The treatment approach will be determined by a number of factors specific to the patient case.

Aggressive treatment with autogenous or allogeneic stem cell transplantation is recommended for younger patients with RRFL. This is linked to prolonged survival and, in some cases, cure of the disease.

  • Follicular lymphoma classification (REAL classification: grade 1/grade 2, IWF classification: small cleaved cell/mixed small and large cell)
  • Previous treatment regimen
  • Duration of remission from the last treatment
  • Symptoms of the cancer

In all cases, the potential risks and benefits of the therapy should be considered and the appropriate decision made should be based on these factors.


Single-agent chemotherapy can be effective in the treatment of progressive or relapsed follicular lymphoma. Agents that may be used in therapy may include:

  • Fludarabine
  • 2-chlorodeoxyadenosine
  • Cyclophosphamide
  • Chlorambucil
  • Doxorubicin
  • Mitoxantrone

However, multi-drug regimens are often more effective in treating relapsed follicular lymphoma. There are several possible drug combinations that may be used, such as:

  • CHOP: cyclophosphamide + doxorubicin + Oncovin + prednisone
  • CVP: cyclophosphamide + Oncovin + prednisone
  • COPP: cyclophosphamide + Oncovin + procarbazine + prednisone
  • FN: Fludara + Novantrone (+/- dexamethasone)

Stem cell transplantation can be carried on in conjunction with high-dose chemotherapy in younger patients; this therapy has the potential to cure the disease. High doses are more likely to destroy the cancer cells completely, but they are also more likely to cause side effects. For this reason, a stem cell transplantation can be used to replenish bone marrow with healthy cells, thus reducing this risk. An autologous (from patient’s own cells) or allogeneic (from a suitable donor’s cells) stem cell transplant may be used.

Targeted Therapy

Unlike conventional treatments that can affect all cells in the body, targeted therapies are designed to specifically target the cancerous cells with minimal impact on the surrounding healthy cells. As a result, there are often fewer side effects associated with this therapy.

Rituximab (Rituxan) is a monoclonal antibody drug, which binds to specific proteins on the surface of the B-lymphocytes, which are the cancerous cells responsible for follicular lymphoma. This marks the cells for destruction by the immune system of the body. As healthy cells do not have the specific proteins on the cell surface, they are not affected.

For patients with RRFL who have previously been treated with rituximab, the likelihood of a positive response with re-treatment is approximately 40%. For those that do go into remission, most tend to have a longer period of remission than the initial response.


Radioimmunotherapy utilizes radiation in combination with targeted therapy to destroy cancer cells, which improves treatment outcomes for RRFL. This involves a monoclonal antibody drug that binds to the antigen protein on the lymphocyte cells so that the radiation is released directly to the affected area. Commercially available radioimmunotherapy drugs include:

  • Iodine 131 tositumomab (Bexxar)
  • Y90 ibritumomabtiuxetan (Zevalin)

Bendamustine (Treanda) can also be used sometimes in the treatment of relapsed or refractory lymphoma.

Combination Techniques

Multi-modality care is a term that refers to the combination of two or more treatment techniques. This is often used in RRFL to increase likelihood or survival and cure of the disease.

For example, chemotherapy is commonly given in combination with a targeted therapy, such as rituximab. This increases the intensity of the treatment and can help improve outcomes with minimal increase risk of side effects. This combination is effective in more than 8 out of 10 patients.


Further Reading

Last Updated: Aug 23, 2018

Yolanda Smith

Written by

Yolanda Smith

Yolanda graduated with a Bachelor of Pharmacy at the University of South Australia and has experience working in both Australia and Italy. She is passionate about how medicine, diet and lifestyle affect our health and enjoys helping people understand this. In her spare time she loves to explore the world and learn about new cultures and languages.


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