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Hi, I'm Ian Flinn. I'm the Director at the Blood Cancer Research Program at the Sarah Cannon Research Institute in Nashville, Tennessee. Today, I'm going to take you through the highlights of my presentation on the BRIGHT trial. The BRIGHT trial was a randomized phase 3 trial, looking at the combination of bendamustine and rituximab in patients versus R-CHOP or R-CVP in patients with previously untreated mantle cell or indolent lymphoma.
In the study, eligible patients were patients with treatment-naïve indolent or mantle cell lymphoma. Investigators first chose whether they receive R-CHOP or R-CVP as their standard therapy. They were then randomized to receive that standard therapy or bendamustine and rituximab. Each patient receives six to eight cycles of therapy and post-treatment, there was an end-of-treatment assessment.
The initial results were published in 2014 and showed that the complete remission rate was 31% with BR versus 25% with R-CHOP or R-CVP. This was designed as a non-inferiority trial, and it was clearly demonstrated that BR was non-inferior to R-CHOP or R-CVP. It also showed that there was a different safety profile where there are increased hypersensitivity reactions with BR and some mild nausea and vomiting in lymphocytopenia, whereas with R-CHOP or R-CVP, there was increased peripheral neuropathy and alopecia and neutropenia. At this analysis, we present the time-to-event endpoints, to include progression-free survival, event-free survival, duration response, and overall survival. This was based on an intention to treat assignment.
There were 224 patients treated with bendamustine/rituximab and 223 patients treated with R-CHOP or R-CVP. Greater than 90% of patients received six or more cycles of therapy. Nearly 45% of patients, in each arm, received rituximab maintenance. This is the progression-free survival by treatment group, as you can see in the orange, which is bendamustine/rituximab. This is clearly superior in terms of progression-free survival to R-CHOP or R-CVP where there's a five-year rate of progression-free survival with 65.5% versus 55.8% in the control arm.
We looked at a subgroup analysis and looked at those patients who had indolent lymphoma versus mantle cell lymphoma. As you can see, the effect is more pronounced in patients who had mantle cell lymphoma versus those patients with indolent lymphoma, where it just reached the borderline of significance statistically. This is the duration of response by treatment group. This analysis was similar to what we saw with progression-free survival. There was a superior duration response with patients treated with BR versus R-CHOP and R-CVP. This was also similar in terms of mantle cell versus indolent lymphoma, as the effects seen with progression-free survival.
We did not see any difference in overall survival by treatment group. Both BR and R-CHOP or R-CVP seemed to be similar in terms of overall survival. This is a forced plot of the time to event variables that I've just reviewed with you. As you can see, they all favor, with the exception of overall survival, they all favor the BR regimen versus R-CHOP or R-CVP. There did not seem to be much of a difference in terms of overall survival of these two different regimens.
Unexpectedly, there was an increased mortality in the patients treated with bendamustine/rituximab versus R-CHOP or R-CVP. There was 40 versus 32 deaths. This was not statistically significant but, however, was numerically worse than the BR arm. The disease progression was the number one cause of mortality in both arms, followed by cardiovascular and infection in the BR arm and, with no one dominant reason, in the R-CHOP or R-CVP patients.
We also looked at secondary malignancies. There was a significant increase in secondary malignancies in patients treated with BR 42 versus 24. However, when we looked at this more in detail, it seemed most of these secondary malignancies were from skin cancers, squamous cell carcinoma of the skin, and basal cell carcinoma. When we excluded these, as well as transformed lymphoma, the differences were less apparent, 22 versus 13 secondary malignancies, which was not statistically significant.
In summary, progression-free and event-free survival in duration of response significantly favored the combination of bendamustine and rituximab versus R-CHOP or R-CVP. This greatest benefit was seen in comparison to R-CVP, as well as in the mantle cell lymphoma subgroup. There is no difference in overall survival seen. The overall safety profile we saw in this updated long-term update of the study was similar to what we had previously reported, except for the higher incidence of secondary malignancies seen in this follow-up. Thank you for your time and attention today.