Published on July 28, 2020
Personalized Medicine in Mantle Cell Lymphoma
What is the standard of care for mantle cell lymphoma? Dr. Peter Martin, Assistant Professor of Medicine in the Division of Hematology/Oncology at Weill Cornell Medical College and a member of the Center for Lymphoma and Myeloma and Patient Power co-founder Andrew Schorr discuss whether treatment for MCL is personalized or if there is one standard of care. "Our goal is to try to individualize therapy and that's because first of all, age in and of itself is not the be-all and end-all of medicine. Anyone with mantle cell lymphoma may be a candidate for more or less intensive therapy as well there's something to be said for patient preferences."
Dr. Martin discusses current studies involving rituximab, immunotherapy options, CAR-T therapy, and autologous stem cell transplants.
UPDATE: On July 24, 2020, the FDA granted accelerated approval to Tecartus (brexucabtagene autoleucel, formerly KTE-X19), the first approved CAR T cell therapy for the treatment of adult patients with relapsed or refractory mantle cell lymphoma.
Transcript | Mantle Cell Lymphoma Standard of Care
Hello, and welcome to Patient Power. I'm Andrew Schorr in California and joining us from New York City at Weill Cornell is the head of the lymphoma service there and that is Dr. Peter Martin, who's an expert in mantle cell lymphoma among other lymphomas. Dr. Martin, thank you for being with us. A lot of patients want to understand how is the standard of care established or changing in mantle cell? How do you see that now?
I think that's a great question. And one of the things that we spend a lot of time talking about, not only in the academic community with community oncologists, but really with every single patient is the fact that there probably is no single standard of care in mantle cell lymphoma. And as oncologists, our job really is to learn as much as we can about the person who has the lymphoma, about the lymphoma itself, and about the constant evolution of potential treatment options, and to try to merge all of those areas to come up with a treatment that makes the most sense for the person that's sitting in front of us at that point in time. The standard that you read in the textbooks are maybe based on age.
For example, it's common for younger people to be told that it's appropriate to be treated with more intensive regimens. So that typically involves high-dose cytarabine (Cytosar-U) based induction treatment followed by some autologous stem cell transplant followed by rituximab (Rituxan) maintenance. And the goal of that treatment is to result in a very long treatment free interval which now is typically in the seven to nine-year range, which is pretty impressive. And it's typical for older people or people somewhere in that 60 to 70-year range and above to be told that a bendamustine (Bendeka) based treatment approach would be pretty common. So bendamustine plus rituximab, there's a little bit less data for rituximab maintenance following bendamustine-rituximab, but I think that that data will eventually emerge and that is commonly being offered now. I mentioned that really our goal is to try to individualize therapy and that's because first of all, age in and of itself is not the be-all and end-all of medicine. People between the ages of... Anyone with mantle cell lymphoma may be a candidate for more or less intensive therapy as well there's something to be said for patient preference.
Some people might prefer a more intensive approach or a less intensive approach. And right now, we don't really have any evidence that that decision impacts longevity or the probability of being around 10 or 20 years from now. And additionally, there are now some more emerging areas of interest where we say, "Well, does everybody necessarily need an intensive approach?" And similarly, does everyone benefit from an intensive approach? So, one scenario for example, is somebody with a more indolent behaving lymphoma, so the lymphoma that's growing very, very slowly. It's possible that those patients might do well with incorporation of novel agents and maybe they don't need chemotherapy at all. Similarly, there's a group of patients who have a higher risk version of mantle cell lymphoma and this might be defined by mutations in TP53, which is a gene that is to some degree responsible for response to chemotherapy. And it does appear that those patients may benefit less from chemotherapy. And so maybe incorporation of novel or targeted agents or immunotherapies in that population might be more beneficial than the standard chemotherapy approaches that I discussed earlier.
So Dr. Martin, let's talk about immunotherapy. We hear about it a lot across cancers now. Does it have a role either in a trial or not for MCL patients?
Immunotherapy definitely has a role in mantle cell lymphoma. The kind of immunotherapy we're talking about may be a little bit different than the kind of immunotherapy that we're typically reading about in the newspaper with respect to other cancers like lung cancer and brain tumors for example. Rituximab was the very first anti-cancer immunotherapy approved way back in 1997. And that has been standard really for most B-cell non-Hodgkin's lymphomas and more and more and more of this data that it is one of the most important parts of anti-mantle cell lymphoma therapy. Not only in combination with other drugs from the frontline setting, but in addition as I mentioned is, evidence for it in the use of maintenance therapy. So two really important trials. One following R-CHOP based therapy in older patients and one following intensive induction and autologous stem cell transplant in younger patients. Both of those trials demonstrated a significant benefit to the use of rituximab maintenance therapy.
As immunotherapy, rituximab definitely has a role in mantle cell lymphoma, another kind of immunotherapy that's emerging are what we call CAR T-cells or Chimeric Antigen Receptor T-cells. This is a more active form of immunotherapy where we use cells that might come from a specific patient or they might come from a donor, and they have been genetically engineered to fight against the lymphoma. It can be transfused into the person with the lymphoma and they have demonstrated now in multiple trials, most recently the ZUMA-2 trial with an agent called KTE-X19 CAR T-cell, and that is clearly active in mantle cell lymphoma, not approved yet, but hopefully will be soon.
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