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.
Management
- 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
GADOLIN study; Lancet Oncology 2016
