John P. Leonard, MD: John, when a new patient comes to you, maybe they’ve had the diagnosis, maybe they suspect the diagnosis, or you’ve gotten a report from the pathologist that it’s mantle cell lymphoma. What do you want to see in that pathology report? What are you talking to your pathologist about? That you want to make sure gets tested before you move forward? And what is the rest of the workup for a newly diagnosed patient?

John M. Pagel, MD, PhD, DSc: I think it’s critically important to make sure that you have the right diagnosis. It’s pretty straightforward in this disease. We should be getting molecular testing and, in particular, we should be looking for overexpression of cyclin D1 and use FISH (fluorescence in situ hybridization) testing to look for the translocation between 11 and 14. Of course, it’s pathognomonic for what we would look for in a diagnosis of mantle cell lymphoma. There are rare cases where we may not see that, but certainly, that helps us feel very good about understanding the diagnosis and in moving forward, from that point.

And you know, patients have to be staged. They need a CT scan for staging. Most everybody will have advanced stage disease if we look hard enough. In fact, that might be seen through using colonoscopies because, of course, about 90% or more of patients will perhaps have gastrointestinal involvement within their disease. Whether they require a colonoscopy or not is controversial. I don’t typically do it, but I know others might, maybe even others here on the panel? Sometimes the diagnosis is made through a routine annual colonoscopy. But the important points include the use of imaging, the FISH test, and, of course, confirming the diagnosis through those ways to stage the patient.

John P. Leonard, MD: Do you do a bone marrow transplant with everyone with mantle cell lymphoma? And do you do a colonoscopy with everyone before and after their first course of therapy?

John M. Pagel, MD, PhD, DSc: Well, I do want to know the risk of the patient. But I’m going to assess that risk largely through the MIPI (Mantle Cell Lymphoma International Prognostic Index) score to understand the proliferative index of the tumor based on the biopsy. Understanding those things usually helps me figure out what I want to do. I don’t typically get bone marrows, and I very rarely will get a colonoscopy.

John P. Leonard, MD: Andre?

Andre Goy, MD: The bone marrow biopsy is important. Sometimes, we see patients that have been diagnosed that don’t have a FISH panel. It allows us to actually perform a FISH panel and then complete the staging. And then, the gastrointestinal workup, with the upper and lower endoscopy, is positive in over 90% of patients at baseline. So, I would recommend to do it at the first restaging, to make sure inhibition was in complete response.

John P. Leonard, MD: I tend not to do bone marrow biopsies unless there are cytopenias or concerns about the cause of cytopenias. I agree that if there is still diagnostic workup to do, that can be useful. I tend not to do colonoscopies because I don’t think that they’re particularly helpful in changing the management in asymptomatic patients, unless they have something on their imaging findings to suggest so. Steve, do you practice in this area?

Stephen J. Schuster, MD: If a patient hasn’t had a colonoscopy in 2 years, I generally do it as part of the staging workup. It’s my habit to always look at where the disease is before you start treatment, and then go back, after you’re done with treatment, to do your response assessment. I have to say, it’s not uncommon for the diagnosis to have been made on a surveillance colonoscopy. As John has said, it’s amazing, for those of us who do hematologic oncology, to see the number of patients in whom it was diagnosed by colonoscopy.

With regard to bone marrow, I agree with what Andre said. Most of the time, we see these patients after a diagnosis has been made, at least at the University of Penn. And so, it’s nice to be able to get viable cells to do metaphase cytogenetics with some B-cell stimulation, and to look at complexity of karyotype. Bone marrow is so frequently positive that if you think it’s somebody in whom you’re worried about maybe needing treatment, or are worried about risk and want to get more information, I’ll do it so that I have viable cells. I always do next-generation sequencing, particularly to look for p53 mutations, because your FISH results may not show you a deletion of p53. But mutation is common. That really sways my approach to the management of patients, if their p53 is mutated. So, I like to have that information if a treatment decision is going to be made.

John P. Leonard, MD: Alexey, what is your practice with regard to bone marrow and endoscopy? Then, maybe you can start to take us into the discussion around the risk profile of your mantle cell patients?

Alexey V. Danilov, MD, PhD: Typically, I would also perform a bone marrow for the reasons that Steve outlined. It typically would be a good source of tissue for molecular studies, as up to 75% of cases see bone marrow involvement. I do not do staging colonoscopies. I was actually curious to know if Stephen recommends random biopsies on a colonoscopy?

Stephen J. Schuster, MD: No. Just visual inspection, biopsy suspicious.

Alexey V. Danilov, MD, PhD: And I think another point is CNS involvement. It’s very rare to see this at diagnosis in mantle cell lymphoma. It typically occurs at relapse, in about 5%, 10% of patients. So, I certainly, unlike in some subsets of diffuse large B-cell lymphoma, do not perform spinal taps at all.

Transcript Edited for Clarity