Insights From: Brad Kahl, MD, Washington University School of Medicine; John P. Leonard, MD, Weill Cornell Medical Center
John P. Leonard, MD: So, assessing a patient with mantle cell lymphoma to see how well they’re responding really depends a bit on the presentation of the patient. If the patient is presenting with cytopenias and a big spleen, obviously one is going to follow the labs, they’re going to follow the patient clinically. If the patient is presenting with big lymphadenopathy, you can obviously follow that on exam. But to a degree, most commonly, patients are getting CT scans or PET scans to assess the degree of response. And I think like with most lymphomas, if over the course of treatment and by the end of treatment, at least induction treatment, the patient is in a complete response—most strictly and rigorously by a PET scan—those are patients who are associated with a better outcome. And so, typically what we would want to see at the end of induction regimen is a PET-negative CT imaging test. Now, again, to not quibble, CT scans can be done as well, and one might argue in some patients you might not need any imaging at all. But in general, we would want to see a negative PET/CT at the end of induction treatment.
Brad S. Kahl, MD: A major area of emphasis in mantle cell lymphoma research going forward will be the incorporation of minimal residual disease assessments into management. There are different strategies that one can employ. One can do flow cytometry, one can do polymerase chain reactions using primers, and now there is a next-generation sequencing technology that can be used for that as well. The challenge is figuring out how to use that information in practice. We know that patients who achieved an MRD-negative remission have achieved a higher quality remission compared to patients who are MRD-positive. We don’t yet know what to do with that information clinically. For example, could you use that information to select patients for maintenance therapy or not, or could you use that information to help escalate or de-escalate treatment. And I think the next generation of clinical trials are going to start addressing those very questions.
I’m not doing MRD assessments in routine practice. We are doing it as part of some ongoing clinical trials that we have.
John P. Leonard, MD: Minimal residual disease is becoming an important area of research for clinical trials. It’s not quite yet ready for primetime as far as treating an individual patient. We know that patients who get an induction treatment of any particular time who go into remission, who are assessed for MRD, and are MRD-negative have a better outcome than those patients who remain MRD-positive. So, clearly, achieving MRD-negative state is associated with a better outcome and one might argue could be a therapeutic target. We are now designing clinical trials to actually ask those questions and getting ready to implement them, saying that if you have a patient who is MRD-negative, is that a patient who you might be able to treat less aggressively because they’re going to do better or perhaps you need to treat them more aggressively because they have sensitive disease?
On the other hand, if a patient is MRD-positive at the end of their induction treatment, that may be a patient who’s more prone to relapse and that may be a patient where we might say, “Well, let’s go on and give more therapy, maybe more intense therapy, because we know that an MRD-positive patient is more likely to relapse in the near future.”