John P. Leonard, MD: Hello and welcome to this OncLive® Peer Exchange® titled, “The Evolving Landscape in Mantle Cell Lymphoma.”
I am Dr John Leonard from Weill Cornell Medicine and NewYork-Presbyterian Hospital in New York.
Joining me today in this discussion are my colleagues: Dr Krish Patel from Swedish Medical Center in Seattle, Washington; Dr Tycel Phillips from the University of Michigan in Ann Arbor; and Dr Andrew Zelenetz from Memorial Sloan Kettering Cancer Center in New York.
Today we are going to discuss a number of topics pertaining to the contemporary treatment of mantle cell lymphoma. We’ll discuss the latest research in the field and the impact of recent clinical trials, including some data from ASH [the American Society of Hematology annual meeting] 2020. These data center around making decisions for treatment selection.
Let’s get started on our first topic. I want to thank all 3 of you for joining us today. It’s I think a timely point to sit and talk about what’s happening in mantle cell lymphoma. We just finished the ASH meeting. There are a lot of exciting new data, and it’s great to be here with you all and get your perspective, so thank you.
The first part of our discussion is centered around the diagnosis and treatment of mantle cell lymphoma. I’m going to ask Andy to give us some key aspects of how mantle cell typically presents itself, what’s the typical course, things around heterogeneity, and how you approach these patients when they first come into your clinic.
Andrew D. Zelenetz, MD, PhD: Mantle cell lymphoma can have a variety of different clinical presentations. It is a very male dominated disease, series run anywhere from 60% to 90% men. But the manifestations can be wide ranging. Early stage disease is quite uncommon. Localized mantle cell lymphoma, though it occurs, is quite uncommon. Most patients have advanced-stage disease presenting as nodal disease, but sometimes can present with non-nodal leukemic phase. Increasingly, we’ve appreciated over the years that all mantle cell lymphoma is not created equal. We have some very indolent behaving disease, where active surveillance is the appropriate initial approach. We have other patients who at diagnosis can have blastic mantle cell lymphoma, which is a very aggressive disease.
There are morphologic features, and so first of all, it’s critically important to get an adequate biopsy; fine needle aspirate is usually not adequate for a biopsy. A core needle biopsy, or preferentially even an incision or excisional lymph node biopsy, will provide the pathologist with sufficient material to make a diagnosis. That’s the foundation of a good treatment plan.
Then once we have that, we do standard staging. Mantle cell lymphoma is typically FDG [fluorodeoxyglucose]-avid. At Memorial Sloan Kettering Cancer Center, we do standard PET [positron emission tomography] scans at baseline. We used to do colonoscopies on everyone because GI [gastrointestinal] tract involvement is extremely common. However, that turns out not to be necessary. It doesn’t fundamentally alter the course. Now, there is such a thing as GI tract-only mantle cell lymphoma. There is presentation as lymphomatous polyposis coli, but that’s usually an incidental finding at a colonoscopy.
The diagnostic work-up is a pretty basic lymphoma work-up. When there’s a leukemic phase, obviously adequate and good quality peripheral blood flow cytometry is necessary. There is supportive and important molecular testing that is necessary. On tissue we would look for the expression of cyclin D1, which is seen in 90% of cases of mantle cell lymphoma. Some variants don’t express cyclin D1, but you have to be very suspicious of a diagnosis of mantle cell lymphoma without cyclin D1 expression. But we can also look for the 11;14 chromosomal translocation.
There are other important biomarkers, the complex karyotype, TP53 mutation, and some controversial data about whether TP53 deletion is important, and we can come back to that as we discuss things a little bit later. Fundamentally, this is a heterogeneous disease. We want to make sure we get an accurate diagnosis so we can formulate a treatment plan.
John P. Leonard, MD: Krish, can you give us a sense of when you see a patient, and you’re trying to think about what to do and how to stage them and look at their risk, what are some of the things you’d look at?
Krish Patel, MD: Yes. As Dr Zelenetz mentioned, limited-stage mantle cell is quite rare, but it’s important to stage those patients appropriately because their treatment pathway might be a little different than those with typical advanced-stage disease.
But what I focus mostly on are some of the prognostic elements that Dr Zelenetz mentioned. What’s the morphology of the mantle cell? Does this patient have blastoid or polymorphic variant? Do they have a high Ki-67? What do their molecular features look like? Do they have TP53 aberrations or not? That helps me to classify that patient and think about what that patient’s risk is. Of course, we have validated scoring systems like the MIPI [Mantle Cell Lymphoma International Prognostic Index] that are often used to classify patients in trials as well, and that incorporates clinical factors such as age, LDH [lactate dehydrogenase], and stage. All of these varying factors I think help to identify different risk groups of patients with mantle cell lymphoma.
John P. Leonard, MD: You mentioned TP53 mutations and deletions. Is that something that you look at in all of your patients that has come into play, can you touch on that? I’m going to ask Tycel when he talks about choosing treatment in a few minutes as well about TP53. But are you doing that in all patients, and would you recommend to the audience if they’re seeing new patients to look for TP53 aberrations?
Krish Patel, MD: Yes, we do. We look for TP53 abnormalities by NGS [next-generation sequencing] in all new diagnoses of patients with mantle cell lymphoma. I’m sure we’ll discuss it, and that can influence our choice of treatments and very much has a major impact on prognosis. We do it for all new diagnoses of mantle cell lymphoma.
Transcript Edited for Clarity