# 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)

Source: https://onco.cc/key-papers/paper-flyer-four-vs-six-cycles-r-chop-lancet-2019/  
OnCo record `paper-flyer-four-vs-six-cycles-r-chop-lancet-2019` (Key paper). 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 did just as well with four rounds of chemotherapy as with six, and had roughly a quarter fewer side effects.

## Summary

An open-label, international, randomised phase 3 non-inferiority trial at 138 sites in Denmark, Germany, Israel, Italy and Norway. It enrolled patients aged 18 to 60 with stage I to II aggressive B-cell non-Hodgkin lymphoma, normal serum lactate dehydrogenase, performance status 0 to 1 and no bulky disease, and randomised them between six cycles of R-CHOP and four cycles of CHOP with six applications of rituximab. No radiotherapy was planned except for testicular lymphoma.

592 patients were enrolled between 2 December 2005 and 7 October 2016, 295 to six cycles and 297 to four; four withdrew consent before treatment, leaving 588 in the intention-to-treat analysis. After a median follow-up of 66 months (interquartile range 42 to 100), three-year progression-free survival in the four-cycle group was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles, with a lower limit of the one-sided 95 per cent confidence interval for the difference of 0 per cent, which demonstrated non-inferiority against a margin of minus 5.5 per cent.

## Fields

- Kind: Key paper
- Last checked: 2026-10-01
- Also known as: FLYER; Poeschel 2019
- Tags: lymphoma-evidence
- Journal: Lancet
- Year: 2019
- DOI: 10.1016/S0140-6736(19)33008-9
- Authors: Poeschel V, Held G, Ziepert M, et al.
- Findings: Three-year progression-free survival with four cycles of R-CHOP plus two further rituximab doses was 96 per cent (95 per cent confidence interval 94 to 99), 3 percentage points better than six cycles.; Non-inferiority was demonstrated against a margin of minus 5.5 per cent.; 294 haematological and 1,036 non-haematological adverse events were documented 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.
- What it means: Four cycles rather than six for young patients with limited-stage, low-risk aggressive B-cell lymphoma. The saving is two cycles of anthracycline and vincristine in people who will live for decades afterwards.
- Caveats: Restricted to patients aged 18 to 60 with normal lactate dehydrogenase, no bulk and performance status 0 to 1: the result does not transfer to higher-risk limited-stage disease.; Recruitment took eleven years, and the chemotherapy standard did not change in that time, but supportive care did.; Radiotherapy was not part of either arm, so the trial does not speak to combined-modality strategies.

## Sources

- Lancet 2019: https://doi.org/10.1016/S0140-6736(19)33008-9
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31868632/
- Europe PMC: https://europepmc.org/article/MED/31868632

## Connected records

- 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/)
- 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/)
- 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: [Non-inferiority trial](https://onco.cc/terms/non-inferiority/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/)
- trials: [FLYER](https://onco.cc/trials/flyer/)
- 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/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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