The Watch-and-Wait Approach in Mantle Cell Lymphoma
Panelists:> Alexey V. Danilov, MD, PhD, Oregon Health & Science University; Andre Goy, MD, Hackensack University Medical Center; John P. Leonard, MD, New York-Presbyterian/Weill Cornell Medical Center; John M. Pagel, MD, PhD, DSc, Swedish Medical Center Seattle and Issaquah>; Stephen J. Schuster, MD, The University of Pennsylvania
John P. Leonard, MD: The next segment of our discussion is really to focus on therapy and how we approach patients. We haven’t talked about it, but I’m predicting that with 5 people who treat mantle cell patients, we’ll get 5 different styles. But I think there’s probably some commonalities and then some differences for the audience to know about.
First is the issue of watch and wait. I think everybody has appreciated that we can now watch and wait, as we do in other indolent lymphomas, in a subset of patients with mantle cell lymphoma. Steve, who do you watch and wait with? Do you monitor everybody for a while if they’re asymptomatic? How do you decide whether or not to embark with this approach for an individual patient, at least for a period of time?
Stephen J. Schuster, MD: I think the only thing more heterogenous than the biology of this disease is the opinions that you get when you ask people how they manage their patients. If we all have different answers to these questions, it means that we’re all right. In any event, I’ll start by saying that whenever I’m not sure what to do, I don’t do anything. I watch the disease and I let the disease tell me what to do, depending on the tempo, and progression, etc. That’s my underlying philosophy with any lymphoproliferative disease, and certainly mantle cell lymphoma which, in the absence of any negative molecular features, can be unpredictable.
Anyway, for watch and wait, I think there’s clearly a role in those that present, as Andre said, with a chronic lymphocytic leukemia-like clinical picture. Splenomegaly, lymphocytosis with CD5-positive B-cells, although the immunoglobulin tends to be brighter on them than with CLL, and those patients tend to be SOX11-negative and have somatic mutations, that’s a no-brainer. You watch them the way you do a CLL patient. In fact, unless they take on some additional cytogenetic events, you can even manage them like a CLL patient. So yes, that’s an easy one.
What about the patient that presents with colon polyps and a little bit of low volume nodal disease? You know, a low Ki-67 score, and no p53 mutations but, obviously, the cyclin D1 rearrangement? I’ll actually watch those patients and look at the tempo of the disease. And most of the therapies in mantle cell lymphoma are, if you look at the Kaplan–Meier survival curves, are in the end, palliative. I don’t know that a delay in treatment of months has negatively impacted on anyone. Obviously if somebody presents with very aggressive features, then you want to intervene before a patient gets sick. I think there’s no harm to watch it.
John P. Leonard, MD: What’s the longest you’ve ever watched a nodal mantle cell patient?
Stephen J. Schuster, MD: I’m glad you asked that, because I learned by lesson from watching a patient. I had a patient, who was a physician, who, in the early 90s, before the description of mantle cell lymphoma was diagnosed with a small to intermediate-sized B-cell lymphoma, had been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). This was in the pre-rituximab era. He became my patient in the mid-90s, when he recurred. We biopsied him and mediastinal nodes showed horrific blastoid mantle cell lymphoma. He was relatively asymptomatic. In those days, we weren’t doing molecular testing. Despite the ugly morphology, I followed him for 11 years before he required treatment.
John P. Leonard, MD: Wow.
Andre Goy, MD: John, you actually were one of the first observers, or your team, with this group of patients that have, beside the CLL-like picture, a low-ball which can be monitored by degree. The median time to treatment is typically 1 year. That gives us a bit of a framework.
John P. Leonard, MD: Yes. Just quickly, Alexey, you started on Ki-67. Do you use that when you see a patient who you’re considering a watch and wait approach for? Will you, if the Ki-67 is 10, watch and wait? And, if it’s 40 or 50, will you not, even if it’s clinically the same? Or do you just kind go based on the clinical guidance?
Alexey V. Danilov, MD, PhD: In my practice, most of the indolent mantle cell lymphomas that I have seen now have peripheral blood lymphocytosis, which, by the way, somewhat derails the MIPI score because leukocytosis is part of the MIPI score. In those patients, I do not test for Ki-67. I do run the minimal workup. In terms of Ki-67 on the lymph node biopsy, I would say that it has rather limited value, overall, in terms of treatment decision. Data from Emory University and Weill Cornell Medical College does suggest that we can watch those patients for up to a year. It’s somewhat controversial, that Ki-67 might contribute to that.
Stephen J. Schuster, MD: It sort of tells me how close to watch them. I don’t think there’s a single laboratory test, by itself, that would make me treat somebody immediately.