MRD Testing in R/R Follicular Lymphoma

Drs Caron A. Jacobson and Krish Patel comment on NGS (next-generation sequencing) and MRD (minimal residual disease) testing in relapsed/refractory follicular lymphoma.

Ian Flinn, MD, PhD: Krish, in a lot of other diseases that we treat, such as in chronic lymphocytic leukemia [CLL], MRD [minimal residual disease] measurement is really important. It’s a new end point for a lot of the trials, and there’s a potential rationale for time-limited therapy. Where are we in follicular lymphoma? Can you measure MRD in patients with follicular lymphoma? Is it useful? Do you change what you do based on those measurements?

Krish Patel, MD: That’s a really important question, Ian. The role of MRD in follicular lymphoma is still evolving. We don’t routinely use it in our practice, outside trials, but there are certainly a lot of interesting data to reflect on. For example, we have data sets about patients who have received radioimmunotherapy who have MRD. We’ve all probably had patients in our clinic who’ve never relapsed post radioimmunotherapy and do very well. It seems to have some powerful prediction in that setting.

More recently, at ASH [American Society of Hematology Annual Meeting], there was a pretty interesting abstract from the group in Madrid that looked at a number of different genetic markers that were present in paired biopsies of individual patients. Investigators looked at using those mutations to really track the course of outcomes in patients, primarily after frontline therapy. So for these patients who are having prolonged remissions, can we use these tools to pick out those early relapses? As they showed in that data set, MRD negativity was associated with very good long-term outcomes.

Just as you pointed out, MRD will have a meaningful role in follicular lymphoma. In regard to challenges, what’s the best tool? For example, in CLL and other diseases we have a lot of circulating cells that serve as a good medium for a liquid biopsy. It’s perhaps not the same in all patients with follicular lymphoma.

Ian Flinn, MD, PhD: It sounds as though we still have some work to do with MRD in patients with follicular lymphoma.

Caron, what about molecular testing of the lymphoma sample? Someone relapses and you biopsy the sample. Are you routinely sending that for molecular testing—next-generation sequencing [NGS]? If you are, what are you looking to do? If you’re not, maybe that’s important as well.

Caron A. Jacobson, MD, MMSc: This is a great question. I think it follows along the MRD testing, where—at least in follicular lymphoma—we’re probably further behind than in some of the other B-cell malignancies. We certainly know of some of the more commonly mutated genes in follicular lymphoma. Some have some prognostic significance, but almost none has an actionable therapy. I don’t know that there’s any decision-making based on those results, except EZH2 mutations, which we’ll discuss later, in terms of whether they are important in relation to some of our newer therapeutic options. I try to get that. You can often do this off a blood sample. So it’s not something that we’re doing off the repeat tumor biopsy, but we are trying to identify some of these mutations using NGS technologies in the blood.

Ian Flinn, MD, PhD: It sounds as though maybe for the current generation of therapies, you’re not finding that to be all that useful. But on a routine basis you do a lot of molecular testing, maybe with the exception of EZH2.

Transcript Edited for Clarity

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