Management of relapsed or refractory follicular lymphoma in adults

BR: bendamustine plus rituximab; CAR-T: chimeric antigen receptor T cell; CR: complete remission; CT: computed tomography; FL: follicular lymphoma; HCT: hematopoietic cell transplantation; PET: positron emission tomography; R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone; R-CVP: rituximab, cyclophosphamide, vincristine, prednisone; RIT: radioimmunotherapy; RT: radiation therapy.

* Clinicians should have a low threshold to biopsy at the time of disease progression to confirm relapse and evaluate for histologic transformation. Signs or symptoms that suggest histologic transformation include:

• Rapid progression of lymphadenopathy
• Infiltration of uncommon extranodal sites (excluding the bone marrow)
• Development of systemic symptoms (eg, fever, weight loss, night sweats)
• Elevated serum lactate dehydrogenase
• Hypercalcemia

Imaging with a combined PET/CT scan can be used to target biopsy at a lymph node with the highest activity on PET.

¶ The management of histologic transformation is based on patient characteristics and disease biology. This is discussed separately.

Δ Patients with asymptomatic recurrent FL do not necessarily require immediate treatment, but they should be followed closely for the development of symptomatic disease. Watchful waiting is unlikely to negatively impact overall survival in this setting.

◊ Patients with early treatment failure after chemoimmunotherapy are unlikely to achieve long-term survival without cellular therapy (CAR-T or autologous HCT). We discuss the possibility of CAR-T cell therapy with eligible patients based on low-quality evidence that suggests that it may result in long-term remission; however, we do not know how the timing of CAR-T cell therapy may impact outcomes long-term, and some patients may elect to postpone cellular therapy until subsequent relapse. Autologous HCT is an alternative for patients who achieve CR. While there is longer follow-up of patients treated with autologous HCT, it is more toxic than CAR-T.

§ For patients without early treatment failure, the choice of therapy depends upon disease tempo, physical status/comorbidities, and preference.

• Patients with a poor performance status may prefer an anti-CD20 monoclonal antibody given as a single agent (rituximab or obinutuzumab) for their relatively low toxicity profile, especially if prior treatment with single-agent rituximab resulted in prolonged remission (eg, >24 months).
• Patients with a good performance status may prefer lenalidomide plus an anti-CD20 monoclonal antibody for its superior response rate despite greater toxicity and no proven improvement in survival rates.
• Patients who relapse following treatment with RT alone for localized disease are treated with a single-agent anti-CD20 monoclonal antibody or chemoimmunotherapy regimens used for the initial treatment of stage II to IV FL.