# FLYER

Source: https://onco.cc/trials/flyer/  
OnCo record `flyer` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Young people with early, low-risk aggressive lymphoma got two fewer rounds of chemotherapy and did just as well, with about a third fewer side effects recorded.

## Summary

FLYER asked the de-escalation question that matters most to a 30-year-old: how little chemotherapy is enough. It enrolled people aged 18 to 60 with stage I or II aggressive B-cell non-Hodgkin lymphoma, a normal serum lactate dehydrogenase, performance status 0 or 1 and no bulky mass, at 138 sites in Germany, Denmark, Israel, Italy and Norway, and randomised them between six cycles of R-CHOP and four cycles of CHOP with six doses of rituximab.

At a median follow-up of 66 months, three-year progression-free survival with four cycles was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles, which established non-inferiority against a margin of minus 5.5 points. The toxicity difference is the point of the trial: 294 haematological and 1,036 non-haematological adverse events in the four-cycle group against 426 and 1,280 in the six-cycle group. Two patients died during study therapy, both in the six-cycle group.

FLYER is why a young person with favourable limited-stage disease is now routinely offered four cycles rather than six, and why the conversation about radiotherapy in that setting is separate from the conversation about chemotherapy duration: no radiotherapy was planned in either arm except for testicular lymphoma.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-10-01
- Also known as: Four versus six cycles of CHOP with rituximab; FLYER trial
- Tags: lymphoma-evidence
- Registry id: NCT00278421
- Phase: 3
- Setting: Aged 18 to 60 with stage I or II aggressive B-cell lymphoma, normal lactate dehydrogenase, no bulk: four cycles of R-CHOP with six doses of rituximab against six cycles of R-CHOP
- Sponsor: German High-Grade Non-Hodgkin's Lymphoma Study Group
- Enrolled: 588
- Result: Three-year progression-free survival 96 per cent with four cycles of R-CHOP plus two extra rituximab doses, non-inferior to six cycles, with roughly a quarter fewer adverse events.
- Outcomes: Progression-free survival at 3 years: Four cycles R-CHOP plus two rituximab 96% vs Six cycles R-CHOP
- Replication: Consistent with the direction of the earlier MInT and RICOVER-60 work from the same group; no independent randomised repeat.

## Sources

- ClinicalTrials.gov NCT00278421: https://clinicaltrials.gov/study/NCT00278421
- Lancet 2019: https://doi.org/10.1016/S0140-6736(19)33008-9

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/)
- fronts: [Chemotherapy](https://onco.cc/fronts/chemotherapy/), [Immunotherapy](https://onco.cc/fronts/immunotherapy/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Monoclonal antibodies](https://onco.cc/technologies/monoclonal-antibody/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rituximab](https://onco.cc/drugs/rituximab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- terms: [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/), [Non-inferiority trial](https://onco.cc/terms/non-inferiority/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [Four versus six cycles of CHOP chemotherapy in combination with six applications of rituximab in patients with aggressive B-cell lymphoma with favourable prognosis (FLYER)](https://onco.cc/key-papers/paper-flyer-four-vs-six-cycles-r-chop-lancet-2019/)
- trials: [POLARIX](https://onco.cc/trials/polarix/)
- 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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