Progress in the Treatment of Follicular Lymphoma - Episode 5

Key Trials in R/R Follicular Lymphoma

John M. Burke, MD:I generally do reserve lenalidomide for patients whose disease has progressed. I will often use it in the second-line setting. The data supporting that choice come from 2 clinical trials. The first is called the AUGMENT trial in which patients were randomly assigned between a combination of lenalidomide and rituximab versus rituximab alone. That study showed almost a tripling of the median progression-free survival and improvement in response rate with the combination of LEN [lenalidomide] plus rituximab versus rituximab alone with an acceptable toxicity profile. The AUGMENT trial was critical in our understanding of the value of the R-squared, which was the lenalidomide-rituximab combination.

The other trial that has informed my practice is called MAGNIFY. This was a trial where all patients similarly received lenalidomide and rituximab in the relapsed setting. The trial has demonstrated an overall response rate in the 70% plus range and a complete response rate in the 40% range. The trial is a little more complicated in that patients are randomized after 1 year of therapy to 2 different maintenance arms, and we don’t know the results of the maintenance component of that trial yet. But certainly, we have several hundred patients treated on MAGNIFY with good outcomes, very similar to those seen in the AUGMENT trial and other earlier studies. Based on those 2 trials, I feel very comfortable offering the combination of lenalidomide and rituximab to my patients with relapsed disease. That can be used in the second-line setting, it can be third-line, it can be fourth-line, or can really be used any time.

As I mentioned earlier, there is a trial called RELEVANCE that compared lenalidomide-rituximab with chemoimmunotherapy in the frontline setting. I discussed that earlier in our discussion here, and it showed good results. The median progression-free survival in the 2 arms was the same, so we know that it’s an effective treatment in the frontline setting. It just doesn’t have quite the long-term follow-up. It doesn’t have an FDA label, and there’s a different toxicity profile. It can be considered for frontline patients, but I would say I would choose it in only the minority of my patients.

The GALEN trial was a phase II trial conducted in France that combined lenalidomide with obinutuzumab. A lot of our data up until now with lenalidomide have used rituximab. As I said, in the AUGMENT, MAGNIFY, and RELEVANCE trials that’s what was used. In other earlier studies, rituximab was the partner for lenalidomide. The GALEN trial built on some earlier studies and did a larger phase II study of the combination of obinutuzumab with lenalidomide and demonstrated a good response rate on the order of 80% overall response rate and complete response rate also in the 40% range.

One of the interesting features of the GALEN trial is that patients who had POD24 [progression of disease within 24 months] did seem to fare better than patients in the MAGNIFY trial. The authors of the GALEN trial pointed that out, that maybe the obinutuzumab antibody partner might be a little more effective than the rituximab antibody partner. I think that’s an unknown at this point. These are different trials with different patient populations. The POD24 group was small in the GALEN trial. The total trial was about 79 patients, and I think the POD24s were only about 20% of those, so those are small numbers on which to be basing major conclusions.

Personally, I don’t know whether obinutuzumab when combined with lenalidomide is better than rituximab when combined with lenalidomide. I’m not sure we’ll ever have a definite answer to that question. I think it’s very reasonable to say a patient who’s received a fair amount of rituximab in the past is now going to go on to a lenalidomide-based regimen to combine it with obinutuzumab. That is now on NCCN [National Comprehensive Cancer Network] guidelines, but it is not a labeled indication for obinutuzumab by the FDA. So it’s reasonable, appears to be safe, has good activity, and that’s where it’s at. I think in my practice, I’ll choose rituximab more commonly to go with lenalidomide. It’s also true in my practice that I’ll choose obinutuzumab earlier in the course than many doctors. So I’m using, as I said, obinutuzumab in the frontline setting. For my patients who have relapsed, I’m still going to be using the lenalidomide-rituximab combination. So, one can use both antibodies in the course of the patient’s disease and their treatment.

Transcript edited for clarity.