Insights From: Brad Kahl, MD, Washington University School of Medicine; John P. Leonard, MD, Weill Cornell Medical Center
John P. Leonard, MD: There are a number of different patterns of progression in patients with mantle cell lymphoma. And like other lymphomas, particularly the indolent lymphomas, the decision or the plan as to what to do depends a little bit on what the patient had before, what their overall situation is, what their symptoms are, and how well whatever they had before works. So, patients often present in a similar fashion to how they initially presented—lymphadenopathy, cytopenias, perhaps splenomegaly. Really a broader range of presentations or presentations of relapse are how patients declare themselves from the standpoint of having relapsed disease.
And so, the approach that would guide our therapy really relates to A) Does a patient have symptoms and low tumor burden, nonbulky disease? In those cases, we may watch and wait. B) Is a patient symptomatic and need treatment? And if so, what is the pattern of their relapse with respect to the time from their previous therapy? Did they have disease that took a long time to relapse, several years, or did they progress within a short period of time with their prior therapy? And obviously, that acuity or that rapidity of relapse may influence how likely we are to watch and wait versus move sooner rather than later to treatment. And then finally, the overall condition of the patient—are they elderly, are they young, what did they have before—might influence our decision into how to proceed.
Brad S. Kahl, MD: The management of relapsed lymphoma depends on a whole variety of factors: how old is the patient, how healthy is the patient, what did the patient get as their initial treatment for mantle cell lymphoma, and how well did that treatment work? And so, it’s hard to really give a blueprint approach for how you would manage relapsed mantle cell lymphoma. But just to make some general broad statements, this is where targeted agents are really having an impact. So, we have several agents that are approved for use in relapsed mantle cell lymphoma.
We have the proteasome inhibitor, bortezomib, we have Revlimid (lenalidomide), and we have ibrutinib, all targeted agents that are approved for use in mantle cell lymphoma. In Europe, they have temsirolimus as well. So, these are all useful agents for the management of relapsed mantle cell lymphoma. Of those, I think ibrutinib is the most active, has the highest response rate, and has the best safety and side effect profile. And so, that’s a very commonly utilized strategy for relapsed mantle cell lymphoma. Having said that, ibrutinib responses don’t last forever, and so you need to have other options for those patients.
Other things that can be considered for relapsed mantle cell lymphoma are things like stem cell transplantation. Allogeneic stem cell transplantation appears to have curative potential for relapsed mantle cell lymphoma. The problem is the risk. There is about a 20% to 30% chance of dying from a transplant-related complication in the first 2 years after that strategy. So, it’s a high-risk, high-reward approach. For young patients, though, I think that should be offered as an option. If you’re 58 years old with relapsed mantle cell lymphoma, the odds of making it to age 65 or 70 are not very good. And so, taking this high-risk approach of the allogeneic stem cell transplant may actually become your best option if you’re a young patient with relapsed mantle cell lymphoma.
John P. Leonard, MD: In the relapsed setting, the younger, fit patient may be approached in a couple of different ways. I would say that if such a patient had extensive prior therapy, if they had been treated aggressively, maybe had an autologous stem cell transplant as part of their initial treatment, had a long remission, and had relapsed with relatively low tumor burden disease, that may be someone we would watch. That may be a patient where we might treat less aggressively, giving them something like lenalidomide or ibrutinib. On the other hand, that may be a patient where we would also consider something like allogeneic transplant at some point. And so, for those issues in follicular lymphoma in the relapsed setting, there are a range of options, and some of that really depends on the pace of the disease and the patient’s clinical preferences. So, for more aggressive disease, I might be thinking more aggressive treatment. For less aggressive disease, slow progression, I might be thinking less aggressive treatment, keep the disease quiet.
Allotransplant has an interesting role in mantle cell lymphoma, and I would say it’s not extremely well defined as to exactly when and for whom one performs an allotransplant. Some people would argue that if you’re going to do a transplant, you should do an allotransplant because that is what’s going to give you the possibility of a cure. That being said, many patients who are candidates for allotransplant—meaning younger and fitter, generally speaking—are going to probably end up getting an autotransplant before they get an allotransplant. But again, these are different preferences, different patterns of disease.
So, I would typically consider an allotransplant in a patient with mantle cell lymphoma who is fit and a candidate for transplant, who has relapsed disease, probably in someone who at least had prior autotransplant and relapsed later or in someone where the disease was becoming a little bit more resistant, less chemosensitive, and had been through a couple of prior therapies. And the concern was that the standard therapy, such as chemotherapy and some of the biologics, perhaps weren’t likely to give a very long remission, and therefore, considering allotransplant might make more sense with the hope of a much longer-term remission where the risk of the allotransplant might be more justified.
Brad S. Kahl, MD: The management of older mantle cell lymphoma patients is particularly challenging because it’s a bad disease and all of the useful agents have a fair bit of toxicity associated with them. And so, the elderly patient certainly is not a candidate for intensive treatment, may not tolerate bendamustine-based regimens very well. This is where some of the new targeted agents might turn out to have a very useful role. So, ibrutinib does not have a frontline indication in mantle cell lymphoma, but that, I think, would be an option for an elderly frail patient—single-agent ibrutinib or ibrutinib combined with rituximab, which is generally more well tolerated than traditional cytotoxic agents. Lenalidomide/rituximab is also a very useful combination for relapsed mantle cell lymphoma and I think certainly could be considered in an elderly frail patient as a frontline option if they’re really not appropriate for standard cytotoxic chemotherapy.