Insights From: Michael L. Wang, MD University of Texas MD Anderson Cancer Center
Michael L. Wang, MD: In general, lymphoma is a very sensitive tumor to treat. We are talking about MRD. For a lot of solid tumors, it’s very hard to get patients into a complete remission. There is still tumor left, so it’s very hard to use the word “MRD” when you can still see the tumor. We feel very lucky when we are treating lymphoma because lymphoma is naturally sensitive to interrogation and we are very lucky to be in this field. Now, we’re lucky that we’re dealing with MRD because we’re able to cause complete remission in many, many lymphomas, either T- or B-cell lymphoma. But let me give you an example of large cell lymphoma and how MRD could help us.
So far, large cell lymphoma could be cured 60% of the time with a frontline therapy called R-CHOP [rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone], with 40% relapse rate. When patients relapse, it is no longer curable, so the mortality rate is 40%. But how do we know who the 40% are and who the 60% are? After you finish frontline therapy, you use MRD. Those people who have MRD positivity very likely belong to the 40%, so the frontline therapy is not enough. You have to add some other therapies to make the MRD go away. So, if that 40% gets reduced to 20%, 10%, and eventually to none, we can use MRD to cure large cell lymphoma. Likewise, we can use MRD in every scenario in other lymphomas.
Peripheral T-cell lymphoma is a frustrating disease to treat, because even after transplant it’s not curable. It comes back. So, after transplant, if we still declare MRD, we’d have to guide the maintenance therapy to cure the MRD to prolong the duration of remission and survival. It’s very useful.
For indolent lymphomas, it’s less useful, because indolent lymphomas—even the tumors there—we don’t have to treat for most of the time, so we watch and then wait. For the high-risk follicular lymphoma, we want to use good therapies to cause a complete remission, then the MRD becomes very handy after that.
MIPI and FLIPI are used at diagnosis. If the patient keeps relapsing, such as with follicular lymphoma, the MIPI is no longer that useful. But MRD becomes very important. MRD is not only a measurement of the amount of the tumor left, but it also tells us which clones are positive. So, for MRD in follicular lymphoma, although it can measure the amount, the most important part is to remember the spin to the sequencing, the cloning. Once we know which clone is active, we know which pathway is overactivated and we can kill that clone with that pathway inhibitor or a combination of pathway inhibitors. So, MRD in this therapy in the field of lymphoma is not only to measure the residual disease, the relapse of the disease, but also to tell us what the disease is sensitive or refractory to. Please remember, MRD has another spin, another quality, to cause cure in this aspect.