Role of Maintenance Therapy in Mantle Cell Lymphoma
Insights From: Brad Kahl, MD, Washington University School of Medicine; John P. Leonard, MD, Weill Cornell Medical Center
Brad S. Kahl, MD: Mantle cell lymphoma is really the most ideal lymphoma to try to exploit maintenance strategies. And I say that because it’s relatively easy to get mantle cell lymphoma patients into remission, but it’s not so easy to keep them there. The remissions are generally short with standard immunochemotherapy approaches. So, the whole notion of a maintenance program is attractive in mantle cell lymphoma. And, in fact, many studies have shown major benefit for maintenance therapy in mantle cell lymphoma.
So, for example, if you have older patients with mantle cell lymphoma, a really large trial done in Europe randomized patients, after R-CHOP chemotherapy, to either maintenance rituximab given indefinitely or interferon therapy. That trial was published in the New England Journal of Medicine and shows a big benefit for the maintenance rituximab therapy, a big progression-free survival benefit, and an overall survival benefit. Based upon that, physicians around the world have routinely started using maintenance rituximab in their older mantle cell lymphoma patients after they finish their induction.
At the same time, we learned that bendamustine might be a better induction platform than CHOP. Most people get BR therapy as their induction, and so it begs the question of whether the maintenance therapy will have the same benefit after BR. A lot of us have just extrapolated the data from the R-CHOP patients, and then in our practices, we will give BR and then maintenance rituximab. Last year at the ASCO meeting, Dr. Rummel presented some data from a trial that they had done in Europe where they randomized patients after BR to observation or to maintenance rituximab. And surprisingly, the trial showed no benefit for the maintenance. The issue I have with that is it was a relatively small trial, only 60 patients in each arm. And if you look in detail at the Kaplan-Meier curves, the shape of the curves is unusual. I’m worried that there are some quirks of small numbers. So, I don’t view that as definitive, but if someone wants to make the statement that there are no data supporting maintenance after BR, that is a true statement. That’s a true statement, although many of us are still giving maintenance after BR because we didn’t view that as definitive.
Now if you flip it to the younger patients, the patients who get intensive therapy—the high-dose cytarabine-containing treatment with the autologous stem cell transplant—it was not known until just recently whether maintenance was still beneficial in those patients. But a large trial that was done in France was presented at the ASH meeting in 2016, and that trial showed a very large benefit for maintenance rituximab after autologous stem cell transplantation, a benefit in terms of progression-free survival, and a benefit in terms of overall survival. So, although those are not published data yet, people are already starting to change their practice based upon the overall survival benefit seen for maintenance therapy in younger patients.
John P. Leonard, MD: So, maintenance therapy in mantle cell lymphoma is a little bit of a controversial issue, in part because the data are not entirely clear for all clinical situations. The fact of the matter is that there are data showing that if you’re using a CHOP-like regimen, that maintenance rituximab offers a benefit including an overall survival benefit. There are other data showing that if a patient has an autologous transplant in first remission, that maintenance rituximab also has an overall survival benefit. Some people interpret that to say that we have 2 scenarios—maintenance rituximab, overall survival benefit—therefore everyone should get maintenance rituximab, extrapolating from those 2 scenarios into others.
Now, on the other hand, I said earlier that bendamustine/rituximab is the most commonly used regimen. And the data that we have up front, suggesting that maintenance does or does not add value, are not very robust. I would say that most people would get maintenance rituximab, but the data supporting that are largely less compelling, and that information or that plan would be more likely based on extrapolation from other data rather than specific well-designed robust studies answering that question. So, in my practice, most patients do get maintenance rituximab.