Follicular Lymphoma: First-Line Treatment Without Chemotherapy for Follicular Lymphoma

Abstract

Opinion statement: The optimal initial treatment of follicular lymphoma (FL) is not known, and initial management of patients varies considerably between providers and institutions. The assertion that patients with low tumor burden can be observed for a period of time is being challenged owing to the safety and tolerability of novel therapeutics and the movement of the field away from traditional chemotherapy agents. Single agent rituximab has become increasingly popular as initial management of patients with low tumor burden disease, and there is evidence that prolonged treatment with rituximab can improve progression-free survival (PFS) when compared to induction with rituximab or observation. Radioimmunotherapy (RIT) has similarly shown efficacy in low tumor burden disease. Novel agents such as lenalidomide, idelalisib, and ibrutinib are being studied in the first-line setting. Importantly, none of these strategies have demonstrated an improved overall survival in a randomized study versus observation. It is the opinion of the authors that endpoints such as PFS alone, while important, should not drive changes in management with limited resources. Composite endpoints including quality of life are more informative on the true impact of treatments on patients with follicular lymphoma. Providers should encourage all patients to be treated in the context of an appropriate clinical trial when possible. If a patient is not a clinical trial candidate, we typically treat patients with advanced stage and high tumor burden with chemoimmunotherapy. The decision to give maintenance rituximab is individualized to the patient, as there is no overall survival benefit. In patients with early stage disease, we favor consideration of radiation therapy if the patient is a candidate. Our initial recommendation to patients with advanced stage, low tumor burden disease, is close observation or "watch and wait." We have observed that most patients become comfortable over time with an observation approach. If a patient is not comfortable with this recommendation, we will use single agent rituximab. If the patient responds to therapy, we do not recommend maintenance rituximab in low tumor burden disease but rather prefer a retreatment strategy or an extended schedule of four additional doses of rituximab.

Risk of secondary haematological malignancies in patients with follicular lymphoma: an analysis of 1028 patients treated in the rituximab era

“…However, bendamustine is an alkylating agent and the risk of secondary malignancies has caused concern (Cheson & Rummel, ). The use of rituximab as a single agent has recently been included in frontline therapy and, in some countries, it has taken the place of immunochemotherapy as a less toxic regimen (Reagan & Friedberg, ).…”

Primary Follicular Lymphoma of the Gastrointestinal Tract: Case Report and Review

“…This treatment modality allows targeted uptake of radiation in tumor cells and has been mostly used in clinical trials [31]. There are some case reports using I 131 rituximab, yttrium-90 ibritumomab tiuxetan, or iodine-131 tositumomab for treatment of recurrent nodal-FL [47,48]. I 131 tositumomab and I 131 rituximab are not available commercially [48].…”

“…There are some case reports using I 131 rituximab, yttrium-90 ibritumomab tiuxetan, or iodine-131 tositumomab for treatment of recurrent nodal-FL [47,48]. I 131 tositumomab and I 131 rituximab are not available commercially [48]. RIT is usually well tolerated as a first line treat ment modality and its major side effect is myelosuppression [48].…”

“…I 131 tositumomab and I 131 rituximab are not available commercially [48]. RIT is usually well tolerated as a first line treat ment modality and its major side effect is myelosuppression [48]. There is no data available on the use of radioimmunotherapy in treatment of GI-FL [31].…”

Open questions in watchful waiting for follicular lymphoma

“…Nonetheless, some questions regarding definitions and endpoints in WW in FL remain unclear. First, given that FL is often a slow growing tumour and patients can live asymptomatically for a long time (even with active disease), progression‐free survival (PFS) is an outcome of questionable value for the comparison of WW and active treatment strategies (Reagan & Friedberg, ). The same argument applies for time‐to‐treatment when comparing WW with any other treatment as it compares delaying therapy (Solal‐Céligny et al , ) with an active treatment upfront, and patients in the WW group can receive the same treatment when they become symptomatic.…”