Follicular Lymphoma

Follicular lymphoma (FL) is an indolent B cell lymphoma of germinal centre origin with t(14;18) BCL2 rearrangement.

• Second commonest lymphoma (20 to 25%), median age 60.

• Graded 1 to 3A (indolent) and 3B (managed as DLBCL).

• FLIPI risk score (age, stage, haemoglobin, LDH, nodal sites).

• Natural history: relapsing course with median survival over 15 years; transformation to DLBCL in 2 to 3% per year.

• Painless waxing and waning lymphadenopathy, often asymptomatic.

• Splenomegaly, marrow involvement, cytopenias.

• B symptoms and rapidly enlarging node suggest transformation.

• Excisional lymph node biopsy (CD20, CD10, BCL6, BCL2; Ki-67 low), t(14;18) by FISH.

• PET-CT or CT, marrow biopsy, LDH, beta-2 microglobulin, hepatitis B.

• PET SUVmax guide for transformation biopsy.

• GELF criteria for treatment.

• Localised stage I to II: involved site radiotherapy 24 Gy (2 x 2 Gy low dose is an option), potentially curative.

• Advanced asymptomatic low burden: watch and wait, or rituximab 375 mg/m2 weekly for 4 doses.

• Treatment indications (GELF): symptoms, bulky disease (over 7 cm), cytopenias, organ compromise, rapid progression.

• Induction: rituximab or obinutuzumab (1000 mg days 1, 8, 15 cycle 1) with bendamustine 90 mg/m2 days 1 and 2 for 6 cycles, or R-CHOP, R-CVP, or lenalidomide plus rituximab (R2: 20 mg days 1 to 21); maintenance anti-CD20 every 2 months for 2 years.

• Relapse: alternative chemoimmunotherapy, tazemetostat 800 mg twice daily (EZH2), bispecifics (mosunetuzumab, epcoritamab, glofitamab), CAR T-cell therapy (axicabtagene, tisagenlecleucel), radioimmunotherapy, PI3K inhibitors withdrawn in many regions.

• Transformation: R-CHOP then autologous transplant for fit patients.

• Supportive: hepatitis B prophylaxis, vaccination, infection prophylaxis, hypogammaglobulinaemia IVIG.