Newly diagnosed and relapsed follicular lymphoma: EHA Clinical Practice Guidelines for diagnosis, treatment, and follow-up

Follicular lymphoma (FL) is the second most common lymphoma subtype in Europe, with a median age at diagnosis of 60-65 years. It is generally considered an indolent disease, and the median overall survival at diagnosis now likely exceeds 20 years. However, considerable heterogeneity exists. Diagnosis requires adequate biopsy material and a specialized hematopathologist. Staging and prognosis rely on positron emission tomography (PET)-computed tomography (CT). Prognostication at diagnosis is based on several validated clinical prognostic scores. Localized disease is usually treated with radiotherapy ± Rituximab. The treatment of disseminated disease includes active surveillance (or in selected cases Rituximab monotherapy) for low-tumor burden patients, and most often immunochemotherapy (or in selected cases chemo-free therapeutic options), ±antibody maintenance in high-tumor burden patients. For relapsed or refractory disease, treatment with Rituximab-Lenalidomide combination ± Tafasitamab or Epcoritamab from the first relapse and single-agent bispecific antibodies, chimeric antigen receptor T-cell therapy (CAR-T) cells, and Zanubrutinib-Obinutuzumab after second relapse should be prioritized over immunochemotherapy. Given the long natural history and risk of relapse, careful follow-up is an important part of patient management. Patients should be actively involved in decision-making. In this guideline, we present current evidence-based recommendations for diagnosis, staging, treatment, and follow-up.