The rationale for rebiopsying patients who have relapsed/refractory follicular lymphoma and the types of molecular information that can be applied to treatment decisions.
Ian Flinn, MD, PhD: Andy, let’s get into the weeds here, in terms of trying to select therapy. Krish brought up early progressors and rapid progressors. When do you worry about histological transformation? Are there things that come to mind that make you want to rebiopsy? Or do you rebiopsy everyone regardless?
Andrew M. Evens, DO, MSc, FACP: There’s definitely some clinical bedside gestalt to this. I definitely don’t biopsy everything. But this is obviously a consideration for anyone displaying more aggressive symptomatology. For example, all of a sudden the patient is having drenching night sweats or other symptoms: a rapidly rising LDH [lactate dehydrogenase], rapidly increasing mass, etc.
It would be tough to put every patient through a biopsy at every relapse. But we do have to think of that, absolutely, because it’s obviously a different prognosis, and different treatment is required. We usually use an anthracycline-based regimen if they haven’t received that. So a biopsy should always come into mind anytime a patient relapses, and you would adjudicate it on that individual patient level.
Ian Flinn, MD, PhD: Are you using PET [positron emission tomography] scanning to help you figure out who you should biopsy and who you shouldn’t?
Andrew M. Evens, DO, MSc, FACP: I am. I know some don’t, but there are some decent older data that support this. We don’t want to be totally chasing SUVs [standardized uptake values], but as you start to get to an SUV above 13, 14, 15, the positive predictive value becomes fairly decent—into the 90s—for diffuse large B-cell lymphoma. I guess you could ask, “What if someone has an SUV of 25? Do you even need a biopsy?” In most cases, I probably still would biopsy. There might be that unique case where it’s a really deep retroperitoneal node, and you’d have to put them through a big surgery. In that scenario, maybe we should skip it. But it has such a negative connotation for prognosis that I would try to biopsy to definitively prove transformation.
Ian Flinn, MD, PhD: Loretta, say you biopsy the patient and it is transformed. Assuming that the patient hasn’t had a prior anthracycline, are you just treating the patient as you would for a regular large B-cell lymphoma, or are you doing anything beyond that?
Loretta J. Nastoupil, MD: That’s evolving. We’ve done some retrospective looks at our database. Patients who’ve not had an anthracycline generally do fairly well, at least more favorably than those who had had CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] for their frontline treatment for follicular lymphoma. That’s made us take pause, in terms of whether we would pursue consolidation with a stem cell transplant. Historically, we had discussed and oftentimes pursued this. Now we’re not doing this as often. That may be the luxury of having more effective treatments at our disposal in the relapsed setting, which you’ll hear more about. But I do think it impacts what we do after anthracycline-based approaches.
Ian Flinn, MD, PhD: What about if someone got R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] in the frontline setting? They had follicular lymphoma and a nice long remission, but now they have transformed. I struggle with what to do here. We don’t really have a proved track record with some of the salvage regimens, even in the frontline setting. Are you taking all those patients to transplant if you’re using a traditional large B-cell salvage regimen? What do you do?
Loretta J. Nastoupil, MD: I agree with you. My optimism around a response with something like R-ICE [rituximab, ifosfamide, carboplatin, etoposide] is relatively low. It depends on the patient’s age, their comorbidities. If they’re someone who I think is going to tolerate an intensive approach, then yes, I might pursue a more traditional relapsed salvage approach. But oftentimes they don’t fall into those camps, so I might pursue something else, like a targeted approach, with all the caveats that they may have a shorter duration of response and still be stuck with that question about auto transplant vs CAR [chimeric antigen receptor] T-cell therapy.
Transcript Edited for Clarity