Minimal Residual Disease Assessment in Lymphoid Malignancies - Episode 6
Michael L. Wang, MD: In the past, we measured MRD using multicolored flow cytometry. We were able to catch 1 malignant cell out of 10,000 normal cells. Now, with newer MRD technologies such as clonoSEQ, we are theoretically supposed to be able to catch 1 malignant cell out of 1 million normal cells. So, we are making headway. If you ask me what the best technology is, let me tell you that I want to be able to fish 1 cell out of 10 million normal cells, even 100 million or 1 billion. If we reach 1 billion, we’ll be able to catch anything before it arrives. We can wipe it out before it becomes anything, so that would be the dream come true. So, 1 cell out of a billion. But that’s a theoretical number. We are so far able to reach, at the current level, 1 out of 1 million cells by clonoSEQ. But clonoSEQ takes advantage of the clonal evolution of the clone. But you have to use a significant amount of material before the tumor.
What’s coming up for MRD in the field of lymphoma is called circulating tumor DNA. So, with CT DNA, you can imagine that our tumor has blood supplies. The blood supplies come from the body. The blood is shared by normal cells and malignant cells. But when the blood flows through the malignant tissue, invariably it gains little DNA fragments due to the high proliferation and the turnover rate of the tumor. Some of the DNA gets shed off into the broad circulation, and it is circulated in our blood. So, that’s where we are implying that most sensitive technologies detect circulating DNA. That’s where the DNA comes from, and there are many, many technologies for that.
One issue with Science Translational Medicine is that 5 papers were published from different institutions using 5 different methods. We know what has been mutated in lymphoma. We use all those genes, and we use the DNA primers to detect all that circulating DNA that belongs to lymphoma. So, we not only can detect minimal residual disease, but we can also know what the tumor has become resistant to, what clone came back, and what belongs to which gene. Using multiple genes for gene mutations, we’re able to specifically measure circulating DNA. This is the most fashionable technology coming up, and it’s very exciting.
Serial PET or CT scans are very expensive and also expose the patient to a lot of radiation. MRD, on the other hand, is just a blood test, so it’s much cheaper, quicker, convenient, and more accurate. MRD, especially with CT DNA, is the future, and it’s going to be realized within 5 to 10 years. I think MRD is the future. MRD will replace the majority of CT scans and PET scans, and even bone marrow biopsies, in the field of a lymphoma. This is very important, and we look forward to that development being widely used in the community.
Transcript Edited for Clarity