# FLIPI, FLIPI2 and POD24 (follicular lymphoma risk)

Source: https://onco.cc/terms/flipi/  
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## TL;DR

FLIPI counts five simple things (age over 60, stage III or IV, more than four node areas, raised LDH, low haemoglobin) to predict how a follicular lymphoma will behave; POD24, relapse within two years of starting chemo-immunotherapy, is the single strongest sign of a dangerous one.

## Summary

What is measured: prognosis in follicular lymphoma. How: FLIPI (2004) gives a point each for age over 60, Ann Arbor stage III or IV, more than four nodal areas, LDH above normal and haemoglobin under 120 g/L, with 0 to 1 low, 2 intermediate and 3 or more high risk (ten-year survival of about 70, 50 and 35 percent in the pre-rituximab series). FLIPI2 (2009) uses beta-2 microglobulin, a node over 6 cm, marrow involvement, haemoglobin and age. m7-FLIPI adds the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, CARD11) from a targeted panel. POD24 is not a score but an event: progression within 24 months of first-line chemo-immunotherapy, seen in about a fifth of patients, whose five-year survival falls to about 50 percent against 90 percent for the rest. Inputs come from examination, PET-CT staged by Lugano, blood tests and marrow. What a result changes: FLIPI does not itself trigger treatment (the GELF criteria for tumour burden do) but stratifies trials; POD24 identifies patients for bispecific antibodies (mosunetuzumab, epcoritamab), CAR-T, lenalidomide with rituximab, tazemetostat in EZH2-mutant disease, and a biopsy to exclude transformation. Where it matters: follicular lymphoma.

## Fields

- Kind: Term
- Last checked: 2026-09-17
- Also known as: FLIPI; FLIPI2; FLIPI-2; m7-FLIPI; Follicular Lymphoma International Prognostic Index; POD24; progression of disease within 24 months; early progression follicular lymphoma; GELF criteria; high tumour burden follicular lymphoma

## Notes

- The molecular layer under the score. The seven genes in m7-FLIPI are not an arbitrary panel: EZH2, CREBBP and EP300 are the chromatin machinery of the germinal centre reaction, and their mutations are the reason a follicular lymphoma cannot complete it. EZH2 Tyr641 substitutions occur in 7.2% of follicular lymphomas and are gain-of-function rather than loss, which is what makes tazemetostat work (Morin 2010); CREBBP or EP300 inactivation is present in about 41% (Pasqualucci 2011); KMT2D is mutated in 89% of cases in the discovery series (Morin 2011). An EZH2 mutation in m7-FLIPI counts towards a lower-risk score and, separately, opens a treatment at relapse, which is a confusing pair of facts worth separating for a patient.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Follicular_Lymphoma_International_Prognostic_Index
- Wikipedia: https://en.wikipedia.org/wiki/Follicular_Lymphoma_International_Prognostic_Index
- Morin et al., Nat Genet 2010: somatic EZH2 Tyr641 mutations in follicular and germinal-centre diffuse large B-cell lymphoma: https://doi.org/10.1038/ng.518
- Pasqualucci et al., Nature 2011: inactivating mutations of the acetyltransferase genes CREBBP and EP300 in B-cell lymphoma: https://doi.org/10.1038/nature09730
- Morin et al., Nature 2011: frequent mutation of histone-modifying genes in non-Hodgkin lymphoma: https://doi.org/10.1038/nature10351

## Connected records

- terms: [Deauville score and PET-adapted therapy](https://onco.cc/terms/deauville/), [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/), [Living with an indolent lymphoma rather than being cured of one](https://onco.cc/terms/lymphoma-living-indolent-lymphoma/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [POD24: progression of follicular lymphoma within two years, and why it changes the plan](https://onco.cc/terms/lymphoma-tx-pod24/), [Prognostic Index for T-cell lymphoma (PIT)](https://onco.cc/terms/lymphoma-pit-score/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/), [Transformation: when a slow lymphoma turns into a fast one](https://onco.cc/terms/lymphoma-bio-transformation/), [Tumour markers (CEA, LDH, chromogranin, thyroglobulin)](https://onco.cc/terms/tumour-markers/), [Watch and wait in follicular lymphoma: being told you have cancer and that nobody will treat it](https://onco.cc/terms/lymphoma-decision-watch-and-wait/), [Watch and wait in lymphoma: when the right treatment is none yet](https://onco.cc/terms/lymphoma-tx-watch-and-wait/)
- drugs: [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Obinutuzumab](https://onco.cc/drugs/obinutuzumab/), [Rituximab](https://onco.cc/drugs/rituximab/), [Tazemetostat](https://onco.cc/drugs/tazemetostat/)
- targets: [CREBBP](https://onco.cc/targets/crebbp/), [EP300](https://onco.cc/targets/ep300/), [EZH2](https://onco.cc/targets/ezh2/)
- cancers: [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- biomarkers: [EZH2 gain-of-function mutation (Tyr646, originally Tyr641)](https://onco.cc/biomarkers/ezh2-y646-mutation/)
- trials: [Mosunetuzumab against rituximab in low tumour burden follicular lymphoma](https://onco.cc/trials/mosun-lbt-fl/), [PRIMA](https://onco.cc/trials/prima-follicular/)
- key papers: [Early relapse of follicular lymphoma after R-CHOP defines patients at high risk for death: an analysis from the National LymphoCare Study](https://onco.cc/key-papers/paper-casulo-pod24-follicular-lymphoma-jco-2015/), [Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial](https://onco.cc/key-papers/paper-prima-rituximab-maintenance-follicular-lancet-2011/)
- roadmaps: [Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting](https://onco.cc/roadmaps/lymphoma-roadmap/)

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