Diagnosis and Risk Stratification of Mantle Cell Lymphoma: Part 1

In this expert roundtable series, Kami Maddocks, MD, The Ohio State University, Columbus, leads a 5-part roundtable panel discussion on updates in mantle cell lymphoma with Jia Ruan, MD, PhD, Weill Cornell Medicine, New York, New York, and Krish Patel, MD, Swedish Cancer Institute, Seattle, Washington.

In the first video of the series, the members of the panel review the latest available data and discuss their approaches to diagnosis and risk stratification of mantle cell lymphoma. 

Transcript:

Kami Maddocks: Welcome to Oncology Learning Network. My name is Kami Maddocks from the Ohio State University James Comprehensive Cancer Center, and I will be moderating today's discussion on mantle cell lymphoma. I am joined today by a distinguished panel of experts in treating mantle cell lymphoma. Would each of you like to introduce yourselves and tell us a little bit about each of your roles? We'll start with Dr Ruan.

Jia Ruan: Thank you so much, Kami. Yes. Hi, my name is Dr Jia Ruan. I'm a lymphoma specialist at Weill Cornell New York Presbyterian Hospital. I take care of patients with lymphoma. I also do a lot of clinical research, focusing on rare subtypes including mantle cell lymphoma. It's really my pleasure to be here today.

Kami Maddocks: It's great to have you. Dr Patel?

Krish Patel: Thank you, Dr Maddocks. I'm Krish Patel from the Swedish Cancer Institute in Seattle. I'm also a lymphoma specialist and have a focus and interest in aggressive lymphomas as well as cellular therapies, and also conduct clinical research in lymphomas including mantle cell. Thanks for having me.

Kami Maddocks: All right. It's great to have you with us as well. Welcome everyone, and thank you for joining us today. Let's kick off our discussion. 

Our first discussion point is going to be on diagnosis and risk stratification. Let's just start by maybe talking a little bit about when a patient presents with a new diagnosis of mantle cell lymphoma. What do you do for testing, or their initial workup?

Jia Ruan: I think it's really the most important question, right? Diagnosis is really the fundamentals of how we take care of patients and also providing very precision based personalized therapy. I want to say that mantle cell lymphoma, it's quite rare. It's only 5% to 8% of all B-cell non-Hodgkin lymphoma, so we really place a lot of stake in terms of its diagnosis.

A majority of the patients present with lymphadenopathy, so we obviously would try to get a tissue biopsy, a lymph node biopsy, and the information on the lymph node biopsy would be immunephenotyping, and see what type of B-cell subtypes. We also would do immunohistochemistry (IHC) looking for cyclin D1 and other markers. I think cyclin D1 is quite specific for mantle cell lymphoma.

On top of that, we do [fluorescence in situ hybridization] (FISH) analysis, and it's translocation 11;14 and for majority of the case. I meant to say that cyclin D1 and translocation 11;14, those are very, very important, almost pathognomonic. So, we have to find those markers in order to anchor our diagnosis. And very briefly, sometimes patient coming with lymphocytosis, we can also do peripheral blood flow analysis, and that could present with us with immunophenotyping, the FISH analysis as well.

Kami Maddocks: And then once you have that diagnosis, what other testing do you recommend, Dr Patel?

Krish Patel: I think just like Dr. Ruan outlined, I think the molecular and genomic profile for patients who have an established diagnosis of mantle cell is very important. In addition to the FISH testing that she mentioned, mutational testing for TP53 can be very important both in terms of prognosis and initial treatment selection. And this is important to assess both for point mutation, which requires [next-generation-sequencing] (NGS)-based testing, but also the evaluation of potential loss of 17p, which can be assessed by FISH as well. And in certain, I think maybe in select cases, perhaps that clinical variant of leukemic non-nodal mantle cell lymphoma, sometimes mutational testing for immunoglobulin heavy chain somatic hypermutation can be helpful as well.

Kami Maddocks: Great. When you talk about TP53, do you always send NGS that diagnosis? Do you resend it at relapse if you send it at diagnosis? Do you sometimes ask for [immunohistochemistry] (IHC)? How are you thinking about testing for TP53?

Jia Ruan: I want to mention that I think it's becoming more and more aware—at least from a provider standpoint, not only in academic centers; I'm hoping that expanding to the community practice as well—that it's quite important as a prognostic index. So, we've been trying to get TP53 analysis from the get-go, which is the initial diagnosis.

The FISH is important, as Dr Patel mentioned, that it can assess the loss of copy or deletion. We always do NGS in our institution, so that could be done by target sequencing, it can be done institutionally, or there are many other third-party sequencing facilities, and we try to get some information. 

The reason is to help us to guide our treatment planning. Say somebody who has TP53, maybe we would be more alert in thinking about should this patient be a good candidate for conventional chemoimmunotherapy? Could they be a better candidate for novel therapy? Because we do know that they tend to have more resistance or shortened duration of response if they were treated with chemoimmunotherapy.

Kami Maddocks: Right. When you're thinking about other testing, what do you order in terms of imaging, particular imaging? Do you do the same in everybody? What imaging do you do? Does everybody get a bone marrow biopsy, endoscopies? What other testing are you thinking of, in either all patients, or certain populations?

Krish Patel: I think that's a great question. Mantle cell can be quite heterogeneous in its clinical presentation, so I think it's important to really think about how you use that information, and how it might change your management. It's pretty rare for us to see mantle cell in a limited stage, but in those clinical circumstances where patients appear to have, say, isolated adenopathy, then I think complete staging which includes a bone marrow assessment, imaging, which should be at least [computed tomography] (CT) of diagnostic quality that often can include a PET scan, and potentially endoscopy can be helpful, as you, I think alluded to, Dr Maddocks. 

Mantle cell lymphoma has a propensity to involve the GI tract. For those cases where we're really trying to establish if somebody might have this rare circumstance of limited stage disease, that can be important. For the majority of patients, we tend to expect that we'll find evidence of mantle cell lymphoma in the bone marrow or the intestinal tract if we look hard enough.

For patients that already have this established diagnosis of, say, advanced stage mantle cell lymphoma, at least by imaging or even by clinical exam, I don't necessarily push for endoscopy or bone marrows in those patients, unless we're also trying to exclude some alternative, say, diagnosis for a symptom like diarrhea. Or if patients present with profound cytopenia that's maybe not explained by things that we would maybe think are obvious explanations, like a very large spleen or things of that sort, then it may be helpful in select cases.

Kami Maddocks: Great. Anything else to add to that, Dr Ruan?

Jia Ruan: I completely agree with what Dr Patel just discussed. I want to just mention that perhaps we also discussed before that there's another biomarker called Ki-67, which is a proliferation index. And it's kind of important initially when we do the diagnosis, because it has some prognostic significance.

To obtain Ki-67, you would kind of have to go for a tissue biopsy, either lymph node biopsy or a bone marrow biopsy. I believe they can also serve that purpose. Peripheral blood, it's good for a diagnosis, but it's very hard to generate your Ki-67. So for somebody who you feel like they would require treatment in the near future, I would try to be aggressive at obtaining some type of tissue biopsy, in order to obtain the Ki-67 index.

Kami Maddocks: Great. We've mentioned TP53 and Ki-67. Are there other things that you look at for prognostication or risk stratification in mantle cell lymphoma?

Krish Patel: I think we alluded a little bit to this entity of so-called indolent mantle cell lymphoma, which is really a clinical diagnosis. And so, these are patients that have been described by Dr Ruan's group at Cornell, that initially often present with lymphocytosis, a minimum of adenopathy, and in many respects can sort of look like CLL, and can be sometimes confused for that. 

The diagnostic testing that Dr Ruan mentioned is important to exclude CLL, but some of these patients can be observed safely without the need for initial therapy. So, that I don't think of as necessarily a diagnostic test, but one of a recognition of a clinical entity that perhaps doesn't require initial therapy.