Treating Mantle Cell Lymphoma: Role of BTK Inhibition - Episode 5

Optimizing Therapeutic Approaches to MCL

Transcript edited for clarity:Eduardo Sotomayor, MD: The factors that I consider before initiation with what type of treatment I’m going to use are basic: the patient performance status and how aggressive or not the disease is. Let me start by saying, these are diseases that affect patients of every population. It’s more commonly in men than in women, and that’s another difference between mantle cell lymphoma and other types of lymphomas. It is 3 to 4 times higher risk in men compared with women.

So first, is this an elderly population? If the disease is aggressive, I would try to see how fit the patient is to receive my therapy. So if the patient is fit, I will consider the patient with aggressive disease for chemoimmunotherapy induction treatment. I will consider the patient for autologous transplant as consolidation and then follow with maintenance rituximab because that sequence has shown to improve overall survival as a frontline therapy for a patient with mantle cell lymphoma.

So unfortunately, this is not for everybody. The majority of patients are not going to be eligible for autologous transplant, so we are looking for treatments that the patient is going to be able to tolerate, treatments that are going to be able to induce response. Particularly, I use maintenance rituximab in those patients who are not a candidate for transplant. There is long-term follow-up from a German group that we are going to discuss later that shows that patients who receive R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone] induction followed by maintenance rituximab do improve progression-free survival and overall survival. So I think it’s important to keep that in mind.

Bijal D. Shah, MD: The first thing I need to make sure I clarify is that maintenance approaches are applicable for both elderly and younger patients. And we have 2 large trials to inform those decisions. The first is by Kluin-Nelemans. This is the New England Journal of Medicine paper in which R-CHOP followed by R maintenance seemed to come with a benefit in progression-free survival and overall survival. This absolutely informs my therapy, and if you look at those survival plots, they’re almost what we were seeing with autologous transplant followed by the Nordic regimen in younger patients, in those under 65. That’s a big deal, and I think that really tells us something.

The next most important randomized data come from the French, and this is the trial of CHOP DHAP [dexamethasone, cytarabine, and cisplatin] followed by autologous transplant, in turn followed by 3 years of maintenance rituximab in which, again, we’re seeing a very clear improvement in progression-free survival. And so now the real question is, Who don’t we give maintenance to? And based on these results, is there still a benefit for transplant?

I think the next pieces of data to inform this decision making are the data from Brad Kahl and the ECOG [Eastern Cooperative Oncology Group]/Alliance group, looking at VCR-CVAD [bortezomib, rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone]. In their study, it just so worked out that patients came off the protocol, and about half ended up going to transplant and half ended up going to maintenance rituximab. Again, this was not a randomized trial. This was not a planned randomization, but it’s the way that it panned out. Interestingly, the older patients tended to go to rituximab, so if anything, they were a higher-risk population. But otherwise the groups, by virtue of their inclusion and exclusion criteria, seemed to be pretty well balanced. And there was no clear benefit for the autologous transplant.

There is an ongoing Alliance trial. Tim Fenske is going to be running this, and this is going to, hopefully, answer this question. And it’s basically saying, “Independent of your induction—you wanted to give R-CHOP, BR [bendamustine plus rituximab], Revlimid, Rituxan—we’re going to assess MRD [minimal residual disease], and if you’re MRD negative, we’re going to randomize you to rituximab maintenance versus autotransplant and rituximab maintenance. If you’re MRD positive, we’re going to use autologous transplant and rituximab maintenance.” We feel that, “OK, there’s still enough disease left behind after your induction that we want to try to deepen that if we can,” so there won’t be a randomization there. But I think we will learn from the randomized approach that is there a benefit for further intensification in these patients and what is the magnitude of that benefit. So it’s a very cool trial, one from which I’m looking forward to seeing the results.

Transcript edited for clarity.