Treating Mantle Cell Lymphoma: Role of BTK Inhibition - Episode 3

Distinguishing MCL From Other Lymphomas

Transcript:Eduardo Sotomayor, MD: Mantle cell lymphoma is a distinct entity biologically in terms of natural history and in terms of response to treatment. Unlike other lymphomas, mantle cell lymphoma has a specific hallmark for the disease, which is the translocation 11;14. And because of that translocation, there is this overexpression of a protein named cyclin D1 that is going to drive proliferation of these malignant cells. But also, now we know that although it is the hallmark, by itself it is not sufficient to induce a clinically aggressive mantle cell lymphoma. There are additional abnormalities.

So more recently, by next-generation sequencing, we know that there are the specific mutations that confer more aggressiveness in mantle cell lymphoma. And these mutations are different from mutations that we are seeing in other types of lymphoma. So that is in terms of the biology.

So in terms of the natural history, mantle cell lymphoma is a disease that responds quite well to treatment. But eventually all the patients will relapse. However, I think that we are going to be discussing today how we are making inroads in trying to change that natural history. And I can say that yes, we are changing the natural history based on the new therapies that we have available. So in terms of treatment response, as I said, there are great responses, but then when the disease relapses, we start to run out of options. But that is also changing.

In the diagnostic work-up, and this is true for all lymphomas, we always like to have a biopsy of an excised lymph node. In other words, we want to collect a lymph node from the patient because it is going to allow us to see the disease in the context of the whole lymph node. But there are situations in which we cannot obtain a full lymph node. For instance, if there is a lymphoma just on the chest or just in the abdomen, then in that situation we need to pursue other ways to get tissue to make a diagnosis. So tissue is extremely important. And then in that tissue, we are going to look at the characteristics of the cells. And also we’re going to do additional tests: flow cytometry, cytogenetics, and, importantly, FISH [fluorescence in situ hybridization]. So FISH in a study that is going to detect that translocation that I mentioned is the hallmark of the disease. The translocation 11;14 is going to be detected by FISH in almost 100% of the patients.

So those are, I would say, the initial tests, and then we need to do a staging. Is the disease in 1 site or in multiple sites? And then we are going to be performing a CT [computed tomography] scan or a PET [positron emission tomography] scan or bone marrow biopsies when indicated. In a patient who has symptoms, gastrointestinal symptoms, we also do an upper and lower endoscopy because this lymphoma has a tendency to be in that gastrointestinal tract. And that’s another difference between mantle cell lymphoma and other types of lymphomas.

In terms of molecular testing, there are several types that we perform at the time of initial diagnosis. We perform FISH in order to detect that 11;14 translocation. So we perform cytogenetics. And in these days, in my practice, I prefer to have cytogenetics that have the fullest spectrum of abnormalities. Although it’s not prime time, in some cases, next-generation sequencing looking for specific mutations or other abnormalities could be indicated. But again, this is not routine practice; this is more in the context of clinical trials.

Now, another test that is evolving is what we call evaluation of minimal residual disease, or MRD. Again, these are tests that are being used more commonly in other types of lymphomas, in other types of leukemias. I think that we are going to be seeing more and more in mantle cell lymphoma, specifically in the context of clinical trials to make decisions on whether patients should continue in therapy forever but also in terms of which patients we should have stopped therapy in because we have a deep molecular response.

Transcript edited for clarity.