Good morning ladies and gentlemen, I’m pleased to present to you the final results of our FLYER trial on behalf of the German Lymphoma Alliance. In the FLYER trial we investigated the randomised comparison of four cycles of R-CHOP plus two cycles of rituximab versus six cycles of R-CHOP in young patients with favourable prognosis of diffuse large B-cell lymphoma.
With regard to the background, we know from the MInT trial that there is a patient population with an excellent prognosis. Those patients present with an age-adjusted IPI of zero and in the absence of bulky disease. Those patients had a three year progression free survival of 95% in the MInT trial, therefore it was our aim to investigate in the FLYER trial whether we could maintain efficacy and reduce toxicity by reduction of CHOP cycles. Here you can see the design of our study: patients were eligible for front-line treatment of aggressive lymphoma, B-cell lymphoma, if they were up to 60 years of age, had limited stage disease, an age-adjusted IPI of zero and no bulk, defined as a maximum tumour diameter of less than 7.5cm. Patients were randomised to receive either six cycles of R-CHOP 21 or four cycles of R-CHOP 21 plus two cycles of rituximab.
This is the result for our primary endpoint, progression free survival. The median follow-up time was 66 months. At three years progression free survival after six cycles of R-CHOP was 94% with a 95% confidence interval ranging from 91% to 97%. After four cycles of R-CHOP progression free survival at three years was 96% with a 95% confidence interval ranging from 94% to 99%. As the lower limit of the 95% confidence interval of our experimental arm was 94% it is shown that it is definitely non-inferior to the standard arm, six cycles of R-CHOP.
These are the results for overall survival, there is also no difference between the two arms. At three years overall survival after six cycles of R-CHOP was 98% and it was 99% after four cycles of R-CHOP.
Let’s have a look at toxicity, first of all the total number of haematological adverse events. Six cycles of R-CHOP led to a higher toxicity with respect to local cytopenia and anaemia, both of any grades and also of grade 3-4, in contrast to four cycles of R-CHOP. The reduction was about one-third. Now, coming to the total number of non-haematological adverse events, you see that after six cycles of R-CHOP a total of 1,295 adverse events were reported of any grade and, in contrast, after four cycles of R-CHOP 835 adverse events have been reported. This means an overall reduction of non-haematological adverse events could be reached for about a third. This was the case in the most common adverse events, as paresthesia, nausea, infection vomiting and mucositis, both in toxicities of any grade but also in toxicities of grade 3-4.
To conclude, in younger patients with favourable prognosis of aggressive B-cell lymphoma, efficacy with four cycles of R-CHOP plus two cycles of rituximab is non-inferior to the previous standard of six cycles of R-CHOP. Adverse events with four cycles were reduced by about a third which means a significant benefit for patients. The relapse pattern is similar in both arms with longer follow-up.