Investigational Therapy in Mantle Cell Lymphoma: KTE-X19 CAR T-Cell Therapy - Episode 6

MRD Assessment in Mantle Cell Lymphoma

Michael Wang, MD: I really think MRD [minimal residual disease] is 1 of the most exciting areas in hematologic malignancies, probably in the whole field of oncology. MRD in mantle cell lymphoma is evolving very fast. Not only can we measure the minimal residual disease, but we can also achieve deep, profound molecular remission. Not only that, but we are also able to use the MRD methodology to track clonal evolution. If the patient appears to be relapsing, we can actually catch the relapse at the molecular stage. We can actually use therapies to strike the relapse, to treat the relapse, to attack the relapse—whatever word you want to use—to get rid of the clonal evolution at the molecular stage.

When the patient has a big tumor, it’s very hard to eradicate the whole tumor. But when the patient has a small tumor, we can much more easily eradicate the tumor. But imagine eradicating the evolution of the emerging clones before they can form a tumor mass. That is much easier. We don’t need much therapy. We can track them with MRD, whether they disappeared or reappeared. This will be the next stage of therapy in the next era.

In summary, mantle cell lymphoma therapy has evolved from the use of chemotherapy to the use of chemotherapy-free therapies to a cellular therapy era. But after cellular therapy, we’re going to reach the next therapy, which is the precision medicine era in mantle cell lymphoma. MRD is just 1 of the molecular-type tools we can use to strike relapses early.

We could also use biological and mechanistical studies to track the clonal evolution, especially the single-cell technologies, including single-cell RNA, DNA, proteomics, and to decipher not only the evolution of the tumor cells but also the CAR T cells and, very importantly, the tumor microenvironment. When we reach that age, we can actually find out the clonal evolution of the driver-resistant clones. We know exactly what pathway is upregulated in that driver-relapsed clone, and we can knock it out with precision medicine.

That’s the next era, after the current cellular therapy era. I’m very, very excited. My colleagues and I are in collaboration with many respected colleagues in the field. We think we could cure a population of mantle cell lymphoma within our careers using all the therapies I described above. I am particularly excited that what’s happening in the laboratory and what’s happening in clinical trials are getting closer and closer. In the future, in the near future, laboratories and clinics are not going to be separated anymore. Because to cure diseases such as mantle cell lymphoma, we need the 2 to work together. And we need precision medicine to happen.

Transcript edited for clarity.