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THOMAS HABERMANN: I started the Mayo Clinic lymphoma database in 1985. We have over 31,000 patients in that. We have our MER program and our LEO and SPORE grant. We're able to do just remarkable studies on our own and in collaboration nationally and internationally. We really believe that clinical trials are the way to effect change and the way to affect outcomes in patients. We have a phenomenal group of hematopathologists constantly effecting change in their protocols and adding new tests.
REBECCA KING: One example of that is some of the studies that we've done looking at FISH testing in lymphoma and determining basically that we take a certain approach to FISH testing in diffuse large B cell lymphoma. So for our diffuse large B cell lymphomas, we know that a double hit lymphoma, which has a MYC rearrangement and a BCL2 rearrangement, is a poor prognosis for the patient. So it's very important to identify those. And so we've developed essentially a triage system where first, we FISH for MYC, and then we FISH for BCL2 if the MYC is rearranged.
We also did a study by looking at retrospective data that just doing what's called a MYC Break Apart probe by FISH alone was missing a certain percentage of MYC rearrangements. We determined that adding a dual fusion MYC/IGH probe along with the MYC Break Apart probe upfront would catch about 4% more of those MYC rearrangements that we were missing by just using the MYC Break Apart probe.
So these were patients who potentially were told, you have diffuse large B cell lymphoma, when they should have been told, you have a double hit lymphoma, which is a higher grade lymphoma, which behaves more aggressively and responds better to more aggressive therapy. Because of the now more widespread availability of different genetic testing of the tumor, within pathology we're much better able to understand the biology of these lymphomas and better able to translate that into our diagnoses. So classifications of these diseases are always changing because of that, those discoveries that are being made in the genetic realm.
THOMAS HABERMANN: We're now taking very aggressive disease and taking an immunologic approach. The therapies that are now starting to really impact the relapsed refractory patients after transplant in different settings are the CAR T cell therapies.
YI LIN: For the patients who are treated on the CAR T studies, overall when you look at that, we're talking about complete remission rate in the 30% to 40% range and even higher for more rare type of lymphoma. Now that we've had three, four year follow-up for the patients who's responded, close to 30% to 40% of them have remained in remission for a very long period of time. So now, you're talking about the median overall survival across studies are closer to two, three year range or longer. So that's a dramatic difference. And that's why we think this therapy is so transformative, because there is a potential for a cure for the patients who respond to this treatment.
One of the question is, who are the people to get CAR T therapy? And that, I think is an area of still ongoing challenge and unmet needs, in the sense that it is very individualized, personal medicine. We're taking cells from the patients. We're manufacturing these CAR T from the patient's own T cells. So essentially, each CAR T product is its own batch, its own lot, of living drug. We've started our own manufacturing. So we can make these CAR Ts on site, so you could get them to patients sooner.
There are larger multicenter studies in earlier settings. So now that we know it works after two lines of therapies, there have been randomized study comparing patients to get CAR T versus autologous stem cell transplant in the second line setting. So now, we're trying to move it up one notch.
THOMAS HABERMANN: The hope is that we're going to develop better CARs, more specific CARs, and less toxic CARs. But that is really changing the landscape over the last literally 24 months.
YI LIN: I think this is just the beginning. This is not the end all. What we're seeing is really the very first generation of CAR T and what it can do for patients.
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