Case Discussion: 68-Year-Old With R/R Follicular Lymphoma

Ian Flinn, MD, PhD: I love your discussion, so I’m going to put it to a case. Maybe we’ll get some your thoughts on this.

This is a 68-year-old man with follicular lymphoma who was diagnosed 7, 8, 9 years ago. He’s now had 2 prior therapies. He has previously been treated with bendamustine-rituximab as well as R2 [rituximab, lenalidomide]. He’s being considered for tazemetostat. His last biopsy was 4 years ago.

Caron, I’ll turn to you. How would you approach this? Are you going to rebiopsy this patient? Your choices, as Andy outlined, are probably either a PI3 kinase inhibitor or this drug, tazemetostat. Would it make a difference to you whether the patient was mutated or not? I’d love to hear your thoughts.

Caron A. Jacobson, MD, MMSc: It depends on the urgency for which the patient needs treatment, in terms of how important the EZH2 mutational status is. For a patient who really needs a response, who is very close to having disease that could be quite symptomatic or could potentially impact organ function, I would be much more comfortable treating with an EZH2 inhibitor if they had an EZH2 mutation. I’d be much more confident that they’d have a meaningful clinical response than if they were EZH2 wild type.

I have a patient just like this right now. My patient has very active disease. I did test her, and she was EZH2 wild type, so I chose a PI3 kinase inhibitor instead because I was more confident that she would get a clinical response and that would at least bridge me to the next therapy better.

But if the patient is stable and you could wait to see if they have a response, I probably would reach for something like tazemetostat first because of its safer safety profile, regardless of whether they had an EZH2 mutation. For me, it’s really dependent on how urgently they need a response to the therapy.

Ian Flinn, MD, PhD: Great. Krish, at Swedish Cancer Institute in Seattle, is it a similar approach? What are you doing?

Krish Patel, MD: Yeah, it’s fairly similar. As has been pointed out, this gain of mutation is typically an early clonal event. We’ve started to get that information at diagnosis, so we have it upstream when we might use it. But for patients who have never had that testing, we usually request it. And I agree that it comes back to this question of, what depth of response do you need for the patient that you have? Do you have a patient for whom you’re really looking to that short-term high response rate to provide something meaningful for them? Perhaps that’s a patient who, if they’re mutated, you’re going to treat with this therapy. That’s very similar to our approach.

Transcript Edited for Clarity