The Evolving Landscape in Mantle Cell Lymphoma - Episode 3
John P. Leonard, MD: Before we move to the targeted therapies, I’m going to put you all on the spot. I’m going to give you 4 general scenarios. What’s your typical go-to regimen? We’ve talked about all of the nuances, and we sliced and diced the pie. But I’m going to say, a run-of-the-mill young patient who needs therapies; run-of-the-mill older patient who needs therapy; a blastoid patient who’s fit; and a TP53-mutated patient. You can do that in any order. But those to me are the 4 biggest buckets, so to speak. We all get that it’s complicated, and you might do a little more of this or a little less, or we have our judgment. But most commonly, what are the things that you use for those 4 buckets of patients, recognizing that a percentage of the time you’ll do something different? I’ll start with Tycel.
Tycel Jovelle Phillips, MD: Clinical trials for all 4 cases. If not on trial, the Nordic Lymphoma Group regimen for young/fit, BR [bendamustine, rituximab], assuming that COVID-19 [coronavirus disease 2019] goes away. Blastoid patients, still we would generally consider the Nordic regimen, with the emphasis of trying to get high-dose cytarabine. Patients with TP53 mutation, typically we would give Rituxan [rituximab] and some sort of BTK [Bruton’s tyrosine kinase] inhibitor.
John P. Leonard, MD: And blastoid? Did I miss that? I’m sorry.
Tycel Jovelle Phillips, MD: Blastoid—I’m still trying to get to transplant, assuming that there’s no TP53 mutation concurrent.
John P. Leonard, MD: OK. Andy?
Andrew D. Zelenetz, MD, PhD: For those who are young, fit, no TP53 mutation, I typically will do a LyMa trial-like approach, but we use DHAX [dexamethasone, cytarabine, oxaliplatin], not DHAP [dexamethasone, cytarabine, salt platinum], times 4, followed by high-dose therapy and stem-cell rescue, with 3 years of maintenance, just as it was done on the trial. For the older, less fit, typically we’re going to start with BR [bendamustine, rituximab], again, if not TP53 mutated. For the blastoid, it’s tough. It depends on age, it depends on who they are. But a lot of those patients we’re putting on a trial with ibrutinib and venetoclax, the upfront SYMPATICO trial.
Then for the TP53 mutated, and we can talk a little more about this later, we have specifically a trial with zanubrutinib, obinutuzumab, and venetoclax, which they get for 24 months. It’s specifically for patients with TP53-mutated mantle cell lymphoma that needs treatment.
John P. Leonard, MD: Got it. Krish, your take.
Krish Patel, MD: Yes, very similar. We use the Nordic regimen as well with transplant and maintenance rituximab in young, fit patients; primarily bendamustine, rituximab in older, less-fit patients. Then for both blastoid and TP53-type patients, we’ve usually tried to enroll in a trial, the SYMPATICO trial being one of those. Occasionally we’ll use cytarabine-containing regimens for the blastoid patients who don’t have TP53 mutations.
John P. Leonard, MD: Great. I don’t think I could argue with any of the comments because they’re all reasonable, and that highlights the challenge of mantle cell lymphoma. Some of those regimens have differences of PFS [progression-free survival] versus the other; differences in OS [overall survival] are less clear. But they’re all reasonable things to do, and I think it highlights the challenges of facing patients with mantle cell lymphoma, in general. Before we move on, any changes? If you happen to see a patient with stage I disease, Andy, you reference it’s uncommon. I’ll ask you. What do you do with a patient with stage I mantle cell lymphoma.
Andrew D. Zelenetz, MD, PhD: Mantle cell lymphoma is very radiosensitive. You burn no bridges by taking a radiation approach. I am not a big fan of chemoimmunotherapy with radiation. The data do not really support that the chemoimmunotherapy adds that much. But the radiation can provide certainly short-term, meaning over years, control. And in some patients it will provide what looks like a curative outcome. We have patients out 10 years. But as I said, it burns no bridges. If a patient progresses, we have all the options on the table. We haven’t used up any treatment.
John P. Leonard, MD: All right. Tycel, Krish, any other thoughts about the patients with stage I and how you approach them? Again, not that common, but we always think a lot about them when they come in.
Tycel Jovelle Phillips, MD: No. I whole heartedly agree with everything Andy said. Some of you may not remember, I sent an email out a few years ago. We had a patient with localized blastoid disease, and I got 20 different answers from 20 different people.
John P. Leonard, MD: What did you do, and how did it work?
Tycel Jovelle Phillips, MD: I just radiated, the patient has been in remission since. I didn’t add chemotherapy, just radiation. But everybody gave me a different answer. I don’t know if any them were wrong, but again, they all included radiation. I think what Andy said is completely correct, radiation is very helpful in mantle cell, especially stage I.
John P. Leonard, MD: Right. Krish, anything different?
Krish Patel, MD: No, I agree completely.
John P. Leonard, MD: I’ll echo the comment I think Andy made, with the colonic polyps. We have a number of those patients who can go years and often don’t have any other disease anywhere else for a long time. All mantle cell is not the same obviously.
Andrew D. Zelenetz, MD, PhD: One little twist on those GI [gastrointestinal] cases. Early on we were worried that these were going to bleed when they got treated and such. We almost never see GI bleed, very interesting.
Transcript Edited for Clarity