R2-CHOP for Relapsed Follicular Lymphoma

Transcript:Krishna V. Komanduri, MD: One of the things you mentioned were the combinations of lenalidomide and rituximab. John, you had a nice JCO paper in 2015 and I thought maybe you could tell us a little bit about that study.

John P. Leonard, MD: That was part of an Alliance-led study that we developed in part to start to add new drugs to rituximab in sensitive patients, in patients that had relapsed disease, not refractory disease. The ultimate design of that study looked at single-agent lenalidomide or lenalidomide plus rituximab. So, again, both arms were, in some ways, experimental. It’s important to understand in this trial that these were relapsed patients, not refractory patients. They were favorable-relapsed patients a little more than you would have in some studies by design for a variety of reasons. In these rituximab-relapsed patients or chemotherapy/rituximab-relapsed patients, lenalidomide had about a 50% response rate lasting over 1 year. And then, when you look at the combination of lenalidomide/rituximab, the response rate went up to about 75%, with the progression-free survival being about 2 years. So, clearly, it was a big difference in a relapsed population, not a refractory population.

There’s an ongoing randomized trial now looking at that called the AUGMENT trial. It has some similarities to our study design, but it’s a phase III trial looking, in relapsed-follicular patients, at rituximab alone versus rituximab/lenalidomide. So, we’ll see how that plays out. For other agents, and Leo alluded to this, I would say that ibrutinib is a drug that has activity in follicular lymphoma. We’ve seen a variety of studies in that population, a little bit more data in the more resistant patient population in studies that have suggested that the response rate in a rituximab-resistant population is about 20%—again, meaningful, but lower in some ways—with the PFS about 4 months or so, but some patients going out longer.

On the other hand, as for idelalisib, I would echo Leo’s comments. Although, it does have that indication in the refractory population and probably is a little bit better in the refractory population where the pivotal data with idelalisib are at about 50% at about 1 year. So, with caution in those patients who have been through chemotherapy, I will still use idelalisib in some cases. I think it’s a manageable drug. It’s one that now that we have a pretty good sense of what the toxicities can be. We watch the patient carefully. And, if they’re febrile, we do the appropriate workup, we give pneumocystis prophylaxis, and I think I have a number of patients doing well on it. I wouldn’t throw that out at this point, not that that’s what you were saying, but I do think that in a selected patient population, with careful use, it can be useful.

In my mind, the issue is the duration of the last response. How long did it take the patient to progress? If they have sensitive disease, long prior remission, you can do whatever you want to do. If they have a short remission, they’re becoming refractory, you need to change the modality of treatment. That’s the person where I might be more prone to give something like idelalisib. That’s where I would be thinking about stem cell transplant, which still has an important role in follicular lymphoma. Despite all of our new toys, there are patients who need it. And, I think, the other point to be made for the audience in follicular is every time that patient relapses, you have to think about transformation. You just, at least clinically, in your mind have to look at that patient and say, “Am I worried about transformation? Is their LDH high? Is one disease site out of proportion to the others? If I got a PET scan, is the SUV high? Do they need a biopsy to really chase after that?” That’s the other, I think, take home message: the transformation issue. And, certainly, in those patients, transplant most definitely goes up higher on the list, as well.

Krishna V. Komanduri, MD: As a transplanter, I just want to point out now that we do have very good data now with nonmyeloablative transplantation with very low early transplant-related morbidity/mortality, but we also have moderate to significant rates of long-term graft versus host disease yet really outstanding long-term survival. This is clearly a curative modality.

Leo I. Gordon, MD: I think you can actually begin to identify those patients that you’re thinking about transplant pretty early in the course.

Krishna V. Komanduri, MD: John?

John Byrd, MD: One of the things about idelalisib that makes it attractive versus a lot of the chemotherapy combinations, or lenalidomide even in the refractory patient, is if they’ve had a lot of chemotherapy, and they have cytopenias and it’s not due to something else, idelalisib does not cause cytopenias. And it’s an enigmatic drug in that as you move it earlier in the course of therapy, you tend to see more toxicity. Whereas when you give it to patients who’ve had multiple therapies, it tends to be better tolerated in terms of the LFT abnormalities and potential other side effects. A lot was made of the infectious risk, but that was identified over multiple phase III studies, so a very large number of patients. And the safety signal was in the early work, and it’s just really prophylaxing people when it’s appropriate. I echo your sentiment that some patients can do very well on that drug for a long period of time.

Transcript Edited for Clarity