Just a bit of background: I think you all know that conventional chemotherapy plus immunotherapy is a standard of care in follicular lymphoma; this is so-called R-chemo plus R-maintenance.

We know that follicular lymphoma is characterised by a history of recurrent relapse until the patient ultimately dies from the disease.

We also know that lenalidomide is an immunomodulatory agent with a complementary mechanism when combined with rituximab.

In fact, lenalidomide restores T-cell and NK-cell functions and also restores the immunologic synapse.

It was shown in vitro that it is synergistic with rituximab and also in vivo in R-squared trials in first line and relapse showing very high best CR rates.

So this is why it was decided to compare the R-squared regimen to the R-chemo regimen in a large randomised phase III trial.

This is the trial design.

You see that people in need of treatment, according to GELF criteria, were randomised 1:1 to either R-squared regimen or R-chemo.

In the R-squared regimen lenalidomide was given over 18 months: over an induction period of 6 months and then one year with possibly a diminished dose in case of achievement of CR/CRu and then one year of rituximab maintenance.

In the R-chemo arm I want to make it very clear that the choice of chemo was done per patient and per the investigator pre-randomisation although it was not planned in the trial to compare the different R-chemo to R-squared.

Patients were stratified according to FLIPI, age and lesion size and there were two co-primary endpoints: CR/CRu at 120 weeks, this came from the FLASH results showing that CR30 could be a surrogate for PFS and CR/CRu was slightly stronger as a surrogate in this particular analysis and there was also PFS.

We report here the first interim analysis.

The first co-primary endpoint, CR/CRu, at 120 weeks there was no significant difference for R-squared and R-chemo – 48% versus 53%.

You see that the best CR/CRu rates were 59% for R-squared versus 67% for R-chemo and the best overall response rates were 84% versus 89% and this is all according to the independent review committee.

The second primary endpoint, which was interim analysis of the PFS, here is shown for both the independent review committee, here, there was no difference: 77% at three years versus 78% for R-chemo.

And exactly the same numbers, looking at the sensitivity analysis, of the PFS according to the investigator review.

Those responses were durable after a median follow-up of 37.8 months.

The three year overall survival was excellent, 94% for both arms, but the data are clearly immature for this particular endpoint.

In terms of safety, the safety profile for R-squared and R-chemo were different.

There were higher grade 3/4 neutropenia, 34% for R-squared versus 50%, and febrile neutropenia, 2% versus 6% with R-chemo.

There were also higher grade 3 or 4 cutaneous events, 7% versus 1% with R-squared.

In terms of second primary malignancy which we prospectively monitored the numbers were exactly the same, 7% in R-squared and 9% in R-chemo; in terms of invasive second primary malignancy it was the same.

The number of grade 5 adverse events was 1% in both treatment arms.

So, in conclusion, I think we can say that in this first report of a comparison of R-squared versus R-chemo the results were pretty similar in terms of the two co-primary endpoints.

Of course we are now continuing to monitor PFS and OS but for the first time we have data showing that an immunomodulatory approach is giving similar results to R-chemo in follicular lymphoma and this is a clear path forward for further research.

I would like to thank all the investigators, patients and families.

Here you see the distribution of enrolment according to the different countries.

This trial was sponsored by Celgene and LYSA and I would like to thank also the DMC member that led us to achieve this result.

Thank you for your attention.