Therapeutic Options in Refractory or Relapsed CD20-positive Follicular Lymphoma

European Oncological Disease, 2006;1(2):77-81 DOI:


Follicular lymphoma is one of the most common of all indolent lymphomas. These are less aggressive forms of lymphoma that can take years or even decades to progress. It is also one of the most common types of non-Hodgkin lymphoma (NHL) worldwide, representing around 20–25% of NHL cases, only slightly less common than diffuse large Bcell lymphoma.1 Follicular lymphoma is more common in older people; patients have a median age of 60 years. Nevertheless median survival time is relatively long, often approaching 10 years. Most cases of follicular lymphoma are CD20+.

Treatment Options
Follicular lymphoma is not curable with conventional chemotherapy alone, although initiating treatment provides very good early results with partial or even complete remission. The natural course of follicular lymphoma is characterised by spontaneous regressions in up to one-fifth of cases. Very aggressive treatments, such as myeloablative bone marrow transplantation, might cure some patients but these are often not available for the majority.

According to the European Society for Medical Oncology (ESMO), standard first-line treatment for patients with symptomatic follicular lymphoma is chemotherapy.2 Primary chemotherapy includes combination regimens such as COP (cyclophosphamide, vincristine and prednisone) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or single agents such as fludarabine or chlorambucil. The addition of anti-CD20 antibodies, primarily rituximab, to initial chemotherapy has improved response rate, duration of response, progression-free survival and overall survival, as shown in large randomised trials (see Table 1).3–5 Nevertheless, patients tend to relapse, albeit later and less frequently, but still with a continous relapse pattern.

Treating Relapsed and Refractory Patients
For late relapses of follicular lymphoma, revisiting the primary treatment options is often successful in achieving remission. Furthermore, the use of targeted monoclonal antibody therapy with rituximab has shown considerable single-agent activity, even after failed transplantation, and may be combined with conventional or high-dose salvage chemotherapy.

There have been two randomised prospective trials of concurrent rituximab and chemotherapy followed by sequential rituximab maintenance therapy. In one trial, the German Low-grade Lymphoma Study Group (GSLG) treated patients with fludarabine, cyclophosphamide and mitoxantrone (FCM) plus rituximab, and then randomised responsive patients to observation or fourweekly applications of rituximab at months three and nine. Results showed that the median response duration had not yet been reached for patients on rituximab maintenance, whereas it was roughly 26 months for patients on observation (p=0.035).6