Follicular Lymphoma (FL)


CD10+, CD19+, CD20+, BCL2+, BCL6+

CD5-, CD43-

t(14;18) IGH-BCL2 translocation



Germinal centre B cell is the cell of origin (centrocyte old morphology term)


LN Biopsy

Can see the classic morphology even macroscopically.




CD10+ (marker of GC when present in mature lymphomas)

CD 19+, CD20+, BCL2+, BCL6+





t(14;18) - BCL2-IGH - Almost always present

MLL-2 gene mutated in 90% of FL.



50% of healthy people have circulating t(14;18) cells, but at no increased risk of developing lymphoma. So t(14;18) is a pre-requisite of FL, but is not pathognomonic.

“FL in situ” – may occur in normal patient with circulating t(14;18) cells that happen to be passing through the germinal centre at time of biopsy. Again, no increased risk for developing lymphoma.


MLL-2 (Mixed-Lineage Leukaemia) gene:

Gene for histone acetyl. Most frequent mutation seen in FL. Combined with t(14;18) causes FL in mice.


Great many other B cell receptor pathway mutations have been identified.





  • FL is PET avid. Upstages many people. Good way to exclude patients from radiotherapy only.

  • Exact role unclear and practice varies but NICE recommends PET-CT prior to stage I/II disease where radiotherapy-only treatment is planned (PET will upstage 10-60% of patients)

BM Biopsy?

  • Not necessarily required – Will it change the management?




Current generalized OS is 20 years

Progression of Disease at 24 months (‘POD24’) is an important prognostic cut off, high risk group for those with a PFS shorter than 2 years after 1st line therapy.


FLIPI – calculate at time of diagnosis

  • Age >60

  • Raised LDH

  • Hb <120g/l

  • Stage III or IV

  • 5 or more nodal areas involved


Median PFS based on FLIPI score

  • 0-1      84 months

  • 2          70 months

  • 3-5      42 months





  • Bulk: >5cm? >7cm? >10cm? No single cut, patient-by-patient assessment

  • B Symptoms

  • Cytopenias

  • Organ compromise

  • ‘Growing’ e.g. interval change on repeat CT after 3-6 months

  • (BNLI and GELF both have published ‘criteria to not watch & wait’)



  • The only good quality evidence demonstrating an increase in OS is for the addition of Rituximab to Chemotherapy.

  • Most other data refer to PFS, e.g. no change in OS with R-maintenance.

  • Therefore, in young patients the question is not which treatment is best, but rather which order is best


Stage 1 (or 2 in a single nodal group)

  • 50% cure rate with full surgical excision or radiotherapy (in UK)

  • Stage 2a treated with ISRT —> 10-yr disease-free survival 50% & only 1% relapse with the radiotherapy field, i.e. curative if truly localised disease.

Stage 2 in different nodal group

  • Unusual scenario, patient-by-patient assessment


1st Line in advanced disease

  • Rituximab-Chemo

  • Obinutuzumab-Chemo (Gallium trial)

  • (Not FCR – toxic, too high a TRM rate)

  • (R2 – Rituximab + Lenalidomide – used in USA)


Choice of 1st line chemo

  • CHOP – Previous standard of care. TRM 1% in Gallium trial. ?Waste of anthracycline upfront

  • Benda – Probably better PFS & better tolerated during treatment (fewer neutropenic infections than CHOP). But longer term severe infections in 6 months post treatment —> TRM 5% in Gallium (PCP pneumonia)

  • CVP – lower CR rate and shorter PFS


Choice of 1st line Anti-CD20

  • Rituximab – standard of care, plenty of historical data

  • Obinutuzumab – Gallium trial. Small but statistically significant increase in PFS (NNT = 25 to delay 2nd line treatment). No difference in OS. More toxic, especially in combo with bendamustine.


R-Maintenance post 1st line

  • Every two months for two years.

  • Based on PRIMA trial, which used R-CHOP à Not strictly approved for post R-Benda but we do in East of England.

  • Controversial – medicalizes patients for two years and increases risk of severe infection. Does not alter OS.



  • Recommended if relapse within 2 years of 1st line therapy, i.e. POD24

  • May provide 10-15 year remission


2nd Line if remission >2 years

  • One of the above that had not been used 1st line


3rd Line

  • Clinical trial is first preference.

    • E.g. UNITY – PI3Kdelta/WNT inhibitor / Anti-CD20 / Benda

  • GemCis / DHAP / Bendamustine

  • Not Idelasilib (PI3K delta/gamma inhibitor) – too toxic, CMV/PCP deaths.