Treating Mantle Cell Lymphoma: Role of BTK Inhibition - Episode 4
Transcript:Bijal D. Shah, MD: When we see patients at Moffitt Cancer Center, the first question I ask is, “Does this patient need therapy?” In other words, is this mantle cell lymphoma going to be one that I can watch and wait on safely? One of the features of those patients is they’re typically going to have limited nodal disease. They can have some, but when we see it, the lymph nodes are in the range of 1 to 2 cm. By PET [positron emission tomography], we’re seeing uptakes in the range of maybe 4 to 6 cm, and the patient, importantly, is asymptomatic. Blood counts are more or less normal. We’re not seeing heavy GI [gastrointestinal] involvement, GI bleeding, or anything along those lines. And so this is a patient where I can ask, “Hey, what is the advantage in treating you now versus waiting?” And so I’m going to put that in the indolent category.
The other, more classical indolent mantle cell lymphoma is going to be those patients who present with almost a CLL [chronic lymphocytic leukemia]—like picture, circulating disease with limited to no nodal involvement, maybe modest splenomegaly, 13 or 14 cm in terms of splenic volume. Marrow is going to be involved to some degree but not enough to cause significant cytopenias, and so that falls in line with a patient with CLL whom you would also watch and wait.
Moving from that category into those whom we need to treat—I think this is an evolving area when we talk about frontline therapy. But I think by that, what I’m really trying to ask is, “Who needs chemotherapy, and whom can we approach with a targeted agent?” I think when you see the very elderly patient who’s not going to tolerate chemotherapy, that decision becomes a little bit easier. And now you’re talking about bringing your novel agents forward, and that could include Revlimid, that could include ibrutinib, or that could include acalabrutinib. We do try to get rituximab with these agents. I do think that there are good data for Revlimid and rituximab. I think there are good data from Michael Wang, MD, and his colleagues with ibrutinib and rituximab. And I’m sure that there are data that will be forthcoming with acalabrutinib and rituximab.
The important thing to stress, though, is that ibrutinib/rituximab—and acalabrutinib/rituximab, I should say—were both studies in patients with relapsed mantle cell lymphoma. However, for the patient who’s older, who has more in the way of comorbid conditions where we are worried, they would be a poor candidate for Revlimid. A good example is someone may have a platelet count of 15 by virtue of massive splenomegaly or something along those lines. Not to say that ibrutinib is going to be easy, but Revlimid may be tougher in that patient. And there are other scenarios too. You do need ideally to administer thrombosis prophylaxis, and I use the term need loosely. I think we don’t have a randomized trial to say that the anticoagulation is necessary, but we did see some thrombotic events on the phase II trial that we did with Revlimid and rituximab in mantle cell lymphoma. So it is my practice to give aspirin or Xarelto or something along those lines if need be.
But again, coming back to this patient who may be elderly, may be frailer, may be prone to falls, or these kinds of things, now you’re at the bedside trying to decide whether you use ibrutinib or acalabrutinib with the potential risk of at least contusion or bruising in the setting of falls. We don’t tend to see a lot of severe bleeds with ibrutinib or acalabrutinib. Or do I go down to the Revlimid/rituximab road? And I don’t have an easy answer in terms of making that determination. Some of it is just gut feel. You look at the patient, and a lot of those splenic variants do very well with Revlimid. And so I might try to push for the Revlimid in that situation.
There are other cases in which the ibrutinib is very, very good at provoking lymphocyte egress. And so if you have a patient with a little bit more in the way of nodal disease, if you’re going to use one of these agents frontline off label, then you might try to use that in that situation. But there’s just a gut feel at that point in time in terms of picking between your targeted agents.
Lauren C. Pinter-Brown, MD: I assess responses much the same as how I would in other lymphomas. Most of those patients have had PET scans. I would do PET scans. If I was attempting or needed a complete response, I would repeat the bone marrow if it had been positive. I would do flow cytometry on the marrow as a way of looking at minimal residual disease. And that would primarily be in the younger patients who are perhaps going to autotransplantation as their consolidation therapy.
I think the role of imaging during treatment is much the same as in other lymphomas. I know all of us have our unique ways of how we order imaging, and I have mine. But I think the bottom line is that we would love to see a complete response, even in patients with mantle cell, and we would be using things like PET and CT [computed tomography] scans to assess that response.
Transcript edited for clarity.