Challenges in Treating R/R MCL

Transcript: Michael Wang, MD: The most challenging issue about relapsed/refractory mantle cell lymphoma is that in the patient with newly diagnosed mantle cell lymphoma who has never been treated, we have the opportunity to induce a response that’s more than 10 years, that may achieve 15 years of no relapse. But once mantle cell lymphoma has relapsed, it’s widely regarded not curable anymore. Therefore, you would follow the drug.... Every time you treat a patient with some therapy, it is inevitable the resistance will develop, and then the patient will have relapsed because of the resistance, lost efficacy, lost response. That will eventually keep happening. Every time that happens, there is more drug resistance, and eventually the patient would die from refractory mantle cell lymphoma.

The challenging effect is No. 1, the nature is not curable. The second is a progressive development of resistance. Why? This is because under therapeutic pressure, the tumor cells keep mutating. The genome of the cell keeps mutating, and every time it mutates, there’s generally a new layer of drug resistance. Not only will the resistance keep happening, but along the disease course it is accelerated. Each time the patient is relapsed, the response rate will drop if you treat them with the same drug, and the interval will get shorter. You have a disease acceleration until the end, that we could no longer… That’s the major challenge: If it is not being cured, its nature of drug resistance is accelerated. That’s the major issue.

If we are able to solve the drug resistance issue, we will be able to cure mantle cell lymphoma. If we are able to solve the drug-resistance issue in the hematologic malignancies, such as lymphoma, myeloma, and leukemia, we’ll be able to cure most of the patients. But resistance is very complex. It depends not only on the progressive accumulation of layers or the layer for resistance mutations but also on the tumor microenvironment and the immunology profile of the T cells and B cells. It is very complicated. That’s the challenge.

In 2020, I think we will welcome something like CAR [chimeric antigen receptor] T-cell therapy in mantle cell lymphoma. That is the only therapy that has the potential to overcome the drug resistance, and that’s to put the patient into a longer remission. While we are facing the refractoriness, the incurable nature, and the drug resistance all the time, there’s a light at the end of the tunnel that CAR T-cell therapy may be the therapy we’re looking for—that it would be a fraction of refractory patients, not curable patients into long-term remission. Maybe with more follow-up time, perhaps we shall be able to cure a small percentage. This is all in my imagination. I have no data to support it, but I think the time to start to cure some refractory mantle cell lymphoma is very close.

Transcript Edited for Clarity