Follicular Lymphoma
CD10+, CD19+, CD20+, BCL2+, BCL6+
CD5-, CD43-
t(14;18) IGH-BCL2 translocation
Pathology
Germinal centre B cell is the cell of origin (centrocyte old morphology term)
LN Biopsy
Can see the classic morphology even macroscopically.

Immunophenotype
CD10+ (marker of GC when present in mature lymphomas)
CD 19+, CD20+, BCL2+, BCL6+
CD43-
Cytogenetics
t(14;18) - BCL2-IGH - Almost always present
MLL-2 gene mutated in 90% of FL.
t(14;18):
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.
Staging
PET?
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?
Prognosis
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
Treatment
When?
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’)
What?
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.
Autograft?
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.