Management

Management is dependent on stage of disease as well as grade.
High grade follicular lymphoma (grade IIIb) is treated as diffuse large b cell lymphoma of similar stage (ie. R-CHOP +/- involved field radiotherapy).


Limited Stage Follicular Lymphoma

Radiation therapy is the primary treatment for limited stage disease, where it offers the potential for cure. 10 year survival ranges from 60-80%. There is no benefit from addition of chemotherapy to radiotherapy.
The typical dose is 24-30 Gy with a 6 Gy boost to bulky tumour masses. Involved field radiotherapy is used.
Despite a lack of randomised evidence suggesting improved benefit and the potential risk for adverse side effects, a number of centres utilise systemic immuno-chemotherapy (rituximab, cyclophosphamide, vincristine, prednisolone R-CVP). Case series suggest 10 year survival of 80-90%.
Observation is performed if radiotherapy would lead to unacceptable toxicity.


Advanced Stage Follicular Lymphoma

Advanced stage follicular lymphoma is incurable but remissions can be induced by systemic chemo-immunotherapy. Most patients are in this stage. Prognosis is estimated using the Follicular Lymphoma International Prognostic Index (FLIPI); this is less accurate with the advent of rituximab but still has prognostic significance.
As the aim of treatment is palliation, chemotherapy need not be instituted immediately; a randomised trial compared immediate therapy with observation alone and demonstrated equivalanet outcomes at 6 years.
Indications for chemotherapy include:

  • Symptoms due to bulky disease
  • Symptoms due to extra-nodal disease (eg. pleural/pericardial effusion)
  • B-symptoms
  • Progressive disease

The ideal treatment is with cytotoxic chemotherapy with rituximab. Meta-analysis has proven the superiority of rituximab containing regimens over conventional cytotoxic therapy. Cytotoxic chemotherapy is usually CVP (cyclophosphamide, vincristine, prednisolone), administered with rituximab (R-CVP), with a response rate of 80%.

Other chemo-immunotherapy regimes

A newer regime is bendamustine + rituximab (BR), with no difference to overall survival compared with R-CHOP but with significantly less toxicity. It is not currently available in Australia.
Fludarabine + rituximab has a good response rate but with significantly higher toxicity. Fludarabine, mitoxantrone and dexamethasone with rituximab has the best response rate (close to 100%) but with greatly increased toxicity.
Oral chemotherapy can be used for patients who can not tolerate rituximab.
Local radiotherapy for symptomatic sites is possible and can help palliate symptoms.

Radio-Immunotherapy

Radio-immunotherapy is a current area of interest. Ibritumomab (anti-CD20 with 90Y conjugated) and tositumomab (anti-CD20 with 131I conjugated) have been explored but are not standard recommendations.

Maintenance Therapy

Maintenance therapy is of interest; rituximab improves progression free survival but with increased toxicity rates; there has been no change in overall survival demonstrated. Recommendations are varied; patients who receive cytotoxic therapy alone for induction therapy are more likely to respond to maintenance rituximab and it is usually recommended in this setting. Most patients continue on maintenance rituximab regardless for about 2 years (PRIMA study - every 2 months for 2 years). Longer administration than this has unknown effects.


Refractory Disease

There is no standard treatment; systemic cytotoxic therapy with rituximab is commonly used (usually a diferent schedule). Radio-immunotherapy is a potential option but has not been extensively investigated. Two agents, ibiritumomab and tositumomab, show 60-80% response rates; in those with a complete response median progression free survival is about 4 years. A randomised study of ibiritumomab confirmed superiority over rituximab in terms of response rates but not progression free or overall survival.


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