An update on the management of Follicular Lymphoma – Dr Toby Eyre

Learning points:

  • Follicular lymphoma is a germinal centre derived, low grade lymphoma.
  • Most present with advanced stage disease (as per Ann Arbor)- Must identify early stage disease (1 & localised 2) as potentially curative and management differs.
  • Biopsy: architecture and IHC inc CD10+, bcl6+, Bcl2+
  • t(14;18) common too (leads to deregulated BCL2 anti-apoptotic gene expression)
  • Grading important – (1-3) based on the % of centroblasts per HPF – 3A= centrocytes present, 3B= centrocytes absent (sheets of centroblasts seen)
  • Must ensure 3b is treated as high grade lymphoma
  • FLIPI prognostic score – validated now in the rituximab era – “NoLASH” 1 point for each:
    • No of nodal sites (>4);  LDH raised, Age> 60, Stage 3-4, Hb <120g/L
  • FLIPI2 score needs a BMAT: Age >60, inc B2M, Hb <120g/L, BM involvement, largest diameter node >6cm.
  • PET if stage 1 or localised stage 2 – PET is sensitive for extra nodal sites (but not BM infiltration- do BMAT)- can upstage patients. Also PET if high grade transformation suspected.
  • 50% of patients with FL will have bone marrow involvement – practice varies across U.K. WRT BMAT pre-treatment.


  • Stage 1 disease and localised 2 – cure 60-70% 24 Gy in 12# (FORT study)
  • Stage 2 + in absence cytopenias, bulk disease, constitutional symptoms = active observation
  • Treatment for cytopenias, bulky disease, constitutional sx is not curative for low grade disease. Most patients will relapse with time.
    • Chemo-immunotherapy: anti-CD20 + 
    • Chemo backbone options: Bendamustine if <70 years (PFS with Bendamustine > CHOP or CVP but not OS). > 70 years CVP. CHOP if concerns that high grade transformation
      Gallium study : obinutuzumab vs rituximab with option of chemo backbone. Obinutuzumab had increased PFS but increased toxicity- infection and reaction.
      Higher FLIPI score of 2 derived significant PFS advantage so NICE approved obinutuzumab + chemo plus maintenance  for FLIPI 2
      FLIPI 0-1 use rituximab + chemo + R maintenance. 
  • Maintenance – PRIMA study R-chemo + rituximab for 8 wkly for 2 years. 60% at 10 years no subsequent line of therapy, improved PFS but not OS. Infection risk, especially after BR. SABRINA study – no difference between IV or SC rituximab maintenance
  • No role for autograft 1st line, 2nd Line if progression from first line therapy <2 years. 
  • Relapse within 2 years is poor prognosis – 5 year survival is 50% and represents 1 in 5 patients needing treatment. 
  • Chemoimmunotherapy choice for relapsed FL -depends on what was given first line and how long was the remission.
  • GADOLIN study- refractory/relapse < 6 months since last dose of Rituximab
    Bendamustine obinutuzumab improved efficacy over  bendamustine alone. 
  • Novel agents: 1. Idelalisib/ umbralisib. 2. lenalidomide plus R (AUGMENT study), CAR-T
    Transformed FL:  R-CHOP or anthracyclin based  (max 450mg/m2 of doxorubicin) ICE, GDP, ESHAP. GDP and then auto
Useful links

AUGMENT study; JCO 2019

GADOLIN study; Lancet Oncology 2016

Obinutuzumab for FL; NEJM 2018

FORT study; Lancet Oncology 2014