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): a randomised, phase 3, non-inferiority trial
- Study type
- Clinical trial
- Study name
- FLYER
- Phase
- Phase 3
- Design
- Randomised phase 3 non-inferiority trial, two-arm, open-label, international, multicentre and prospective
- Sample size
- 592 patients enrolled; 588 patients in the intention-to-treat (ITT) analysis
- Source
- The Lancet · 2019
- Trial registration
- NCT00278421
In plain words
In young patients (18 to 60 years) with early-stage aggressive B-cell lymphoma and favourable features, the standard treatment is six cycles of R-CHOP chemotherapy. This study showed that four cycles of R-CHOP plus two extra doses of rituximab work no worse than six cycles; after 3 years, about 96% of patients in the four-cycle group had no disease progression. At the same time, there were fewer side effects in the four-cycle group. These findings apply only to patients with the features described, and treatment decisions should be made with your treating doctor.
Key results
Treatment arms and regimens
Six cycles of R-CHOP. CHOP consisted of cyclophosphamide (750 mg/m²), doxorubicin (50 mg/m²) and vincristine (1.4 mg/m² with a maximum total dose of 2 mg), all given IV on day 1, plus oral prednisone or prednisolone (at the investigator's discretion) at 100 mg on days 1 to 5. Rituximab was given at 375 mg/m² body surface area. Cycles were repeated every 21 days. Radiotherapy was not planned except for testicular lymphoma.
Four cycles of R-CHOP plus two doses of rituximab (six doses of rituximab in total). Drug doses and schedule were as in the six-cycle group: cyclophosphamide 750 mg/m², doxorubicin 50 mg/m² and vincristine 1.4 mg/m² (maximum 2 mg) IV on day 1, prednisone or prednisolone 100 mg on days 1 to 5, and rituximab 375 mg/m²; every 21 days. Radiotherapy was not planned except for testicular lymphoma.
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients aged 18 to 60 years with aggressive B-cell non-Hodgkin lymphoma with favourable prognosis, stage I–II disease, normal serum lactate dehydrogenase (LDH), ECOG performance status 0–1 and no bulky disease (maximum tumour diameter less than 7.5 cm). The study was conducted at 138 clinical centres in Denmark, Israel, Italy, Norway and Germany.
Endpoints
Primary endpoint: progression-free survival (PFS) at three years. The primary analysis was done in the intention-to-treat population, with a non-inferiority margin of -5.5%. Safety was assessed in all patients who received at least one dose of the assigned treatment.
Safety and side effects
In the four-cycle group, 294 haematological and 1036 non-haematological adverse events were recorded, versus 426 haematological and 1280 non-haematological adverse events in the six-cycle group. Two patients, both in the six-cycle group, died during study treatment. The authors concluded that toxic effects were substantially reduced with the four-cycle regimen. The rate of grade ≥3 adverse events is not reported in the abstract.
Clinical significance and place in guidelines
Based on this study, in young patients (18 to 60 years) with aggressive B-cell non-Hodgkin lymphoma with favourable prognosis (stage I–II, normal LDH, ECOG 0–1 and no bulky disease), chemotherapy can be reduced from six to four cycles of R-CHOP (with two additional doses of rituximab) without compromising treatment outcomes and with fewer toxic effects. The status of this approach in current clinical guidelines should be checked separately; the abstract gives no information on its approval or inclusion in guidelines.
Limitations
The study was open-label. The results can be generalised only to young patients (18 to 60 years) with favourable prognosis (stage I–II, normal LDH, ECOG 0–1, no bulky disease). Radiotherapy was not planned except for testicular lymphoma. Other limitations should be checked in the full text.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.