Frontline Therapy for Mantle Cell Lymphoma

Transcript: Ian Flinn, MD: That was a really nice segue into where we should be going with frontline therapies. We’re mostly going to be talking today about the relapsed population, but sometimes the second therapy is dependent on what someone had on the first line. Bijal, let’s talk a bit about some of the initial considerations. We heard about fitness and some of the prognostic factors might vary how you tailor your approach. Could you give me your approach to the initial therapy of patients with mantle cell?

Bijal Shah, MD: Absolutely. The first thing I’m thinking about is, what is the patient presenting with? If it is extensive nodal disease or proliferative disease—a patient who’s symptomatic—I’m asking the question, how can I get them to feel better faster? This is a scenario where I may consider an R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone] or R-DHAP [rituximab, dexamethasone, high-dose cytarabine, cisplatin] regimen for someone who I think can tolerate that regimen. VR-CAP [bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone] is also a good regimen, and it’s something that again can help people feel better faster.

These are things that I’m thinking about in the moment for less proliferative disease. Bendamustine, if they’re symptomatic, will help them feel better much faster, and that’s something I will commonly utilize. For the patient who has extensive disease—maybe they’ve got some mild cytopenias, more of a leukemic presentation—Revlimid [lenalidomide] or rituximab works beautifully, perhaps because of the ability of rituximab to concentrate in the spleen. Revlimid’s ability to drive that immunomodulatory effect may take a bit longer to realize. It’s a very effective regimen. We found that it’s effective even in patients with a p53 mutation, so that’s also something that we like to keep in our back pocket for that subset of patients.

Transplant—I’m a little less convinced how much it adds. We try to look at it for lower-risk patients. I think in higher-risk patients, we all argue that we want to try to get as much as we can, but at least in the lower-risk subsets, we’ve tried to look and couldn’t see much advantage for that intensification. I think these are all things that we need randomized studies to help us better understand and answer.

Ian Flinn, MD: It wasn’t too long ago that people were very dogmatic that you have to do this—you have to use cytarabine. You have to do that. As time goes on, I’m impressed by the fact that there’s not 1 way, and there are many differences. Tycel, what is your take on how you tailor our therapy in the frontline setting for patients.

Tycel Jovelle Phillips, MD: That’s a completely up to the individual. There’s not a 1-size-fits-all therapy. I will take into consideration a multitude of factors—the patient’s fitness, what the patient wishes. Not every patient wishes to proceed to a transplant. Thankfully, nowadays, we have some testing that may also help indicate which patients may or may not require transplantation, based on some of the improvements we’ve been able to make and the depth of response.

For younger, fit patients, historically, our center has used the Nordic regimen, which will take patients to autologous stem cell transplantation. I will say that recently, we’ve tried to tailor things. We’ve been much more involved in clinical trials that are giving novel therapies up front with an aim of trying to evaluate minimal residual disease in this patient group and hopefully avoiding transplantation in this population. Obviously, you don’t have to hit them with a sledgehammer to still get responses in a disease that, to this day, unfortunately, we can’t cure.

Ian Flinn, MD: Yes. I think that 1 of the problems right with the clinical trials we’ve had is that, in the past, it’s been mantle cell lymphomas. It was not all the different subtypes. Trying to tailor this therapy, what we’re not supposed to do is make cross-trial comparisons, right? Trying to figure out what group really benefits from it has been hard. Again, it’s a rare disease. It’s hard to accrue subgroups to different trials.

Tycel Jovelle Phillips, MD: I think some of the benefit that we found from these trials is in the p53-mutated-deleted patients. We know these patients don’t benefit from autologous stem cell transplantation. This is something we didn’t know several years ago, and were still pushing people through. In that conversation, with the tests that we’re getting now, if I have p53-mutated or -deleted patient, we’re not discussing Nordic and transplant. We’re discussing other, novel ways to try to manage the cancer.

Based on some of the data that’s been designed for cross-trial comparison, even if you look at the original R² [lenalidomide, rituximab] data, it’s a smaller patient population, but the long-term outcome looks very good compared with some of these more aggressive regimens that include transplantation. Again, it brings up the question, do we always have to depend on chemotherapy in this type of disease to get good long-term responses? I don’t think any of us really knows that answer for sure, but hopefully it will be something else that teases itself out.

Ian Flinn, MD: If you use chemotherapy up front, are you using rituximab maintenance? If you do transplant, are you using rituximab maintenance?

Tycel Jovelle Phillips, MD: In our transplant patients, we are using rituximab maintenance based on the data that came from the French group. I think that’s the only study thus far that’s showed an overall survival benefit with maintenance rituximab, so it’s hard not to do that in that group of patients.

In patients who receive R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone], I am giving them the maintenance thereafter. For the BR [bendamustine, rituximab] patient group, it’s hit or miss. We have some conflicting data on the original study from Mathias Rummel that didn’t demonstrate any sort of PFS [progression-free survival] benefit, but there were a lot of arguments about how the trial was conducted. There was a poster presented in ASH [American Society of Hematology Annual Meeting & Exposition] 2019 that showed that there does appear—at least retrospectively here in the United States—to be a benefit to maintenance rituximab.

I think that’s really an unanswered question. Again, it’s tailored toward the patient. Do they want to come back every 2 months to get rituximab? They may have had complications like infections and other cytopenias that, in my experience, have come out a lot more with bendamustine than we had previously experienced. These patients are on prophylaxis for antibiotics or acyclovir and Bactrim for years sometimes because I can’t get their CD4 count above 200.

These all factor into the decision, as far as the nontransplant patient. To transplant patients, yes. For nontransplant patients, it’s almost an individualized decision.

Ian Flinn, MD: OK. Javier, is there any role for radiation therapy in mantle cell lymphoma?

Javier Munoz, MD, FACP: In patients who have very early localized disease, the guidelines do suggest that there could potentially be a role for localized radiation. That said, as we discussed previously, most patients with mantle cell lymphoma are going to have advanced disease—bone marrow involvement, gastrointestinal involvement. Hence, they will not be good candidates for transplantation.

Ian Flinn, MD: I was about to say the same thing. It’s really a small group of patients. When you go and look closely—if you did colonoscopies and blind biopsies, you’re likely to have found the disease elsewhere, so it’s hard to find truly localized patients. In that patient population, even some palliation sometimes is helpful for that group of people.

Transcript Edited for Clarity