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)

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.