Immunomodulatory Therapy for FL: The R-Squared Regimen

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Nathan H. Fowler, MD: Lenalidomide is a very active drug in several different types of malignancies. Lenalidomide, as we know, is commonly used in the treatment of myeloma, and about 8 to 10 years ago at MD Anderson, we began exploring combinations of lenalidomide and rituximab in low-grade lymphomas. This was based upon preclinical data that we had gathered at our center suggesting that there was synergy between lenalidomide and rituximab. The idea was that lenalidomide, which had been shown to augment the activity of certain types of immune effector cells, NK [natural killer] cells and T cells, could potentially synergize with a monoclonal antibody like rituximab and increase ADCC, antibody-dependent cell-mediated cytotoxicity. In essence, it could augment the effect of rituximab in low-grade lymphomas. We designed a very early pilot trial looking at this combination in untreated patients with follicular lymphoma. We enrolled 30 patients. Actually, in low-grade lymphomas, we saw very high responses: 98% of patients responded to the combination.

After that trial was announced, there were other trials that were initiated, and also reported, showing very similar overall response rates and complete response rates with the same regimen and the same population of patients with follicular lymphoma. This group of trials, our trial as well as other subsequent trials, then led to a randomized phase III trial called the RELEVANCE trial. This was a trial that was recently completed, which looked at lenalidomide and rituximab versus rituximab plus chemotherapy in patients with follicular lymphoma. It enrolled a thousand patients. We may actually see data from this trial soon, which will look at this new regimen for patients with newly diagnosed follicular lymphomas.

Carla Casulo, MD: The MAGNIFY study showed the use of lenalidomide and rituximab in patients who have relapsed/refractory follicular lymphoma. This was really interesting, because they also looked at a subset of patients who were double refractory to either an alkylator or rituximab or had an early relapse. This was presented at ASCO [American Society of Clinical Oncology] this year. What they demonstrated was that the regimen seems promising and had high response rates. But in the early relapsed population, there was also evidence of a signal of efficacy suggesting that about 50% to 60% of patients responded and the duration of response was about 1 year. So, I think that in this particular population of patients, it might have a promising future.

The phase III AUGMENT study is looking at lenalidomide and rituximab compared to rituximab placebo in patients with relapsed follicular lymphoma. That study is still ongoing. What they’re looking to evaluate is whether or not lenalidomide is an important addition to rituximab in the treatment of patients with follicular lymphoma.

I actually have used lenalidomide and rituximab in patients with relapsed indolent lymphomas, and I find that it is well tolerated. The benefit of it, too, is that you can modify the dose based on cytopenias and side effects, such as rash or fatigue or myalgias, that the patients might experience. I find that the duration of response is actually quite good. Particularly with elderly patients, I find that it’s very easy to administer. So, we certainly do use it quite a bit in patients with relapsed indolent lymphoma.

Transcript Edited for Clarity