Treatment Considerations in DLBCL

John Leonard, MD: I want to ask a practical question, Loretta. The issue is around when the patient has pending FISH [fluorescence in situ hybridization] results. You’re worried about double-hit lymphoma, but you’re not sure. They need to get treated. I’ll give you an example. I was in clinic earlier today, and we have a patient we’re trying to get in quickly. But the record is a patient who’s relatively young, in their 40s, who’s got a big pelvic mass and a Ki-67 of 90%, according to outside records. I’m sure this is a high risk for double-hit lymphoma, based on what’s there. She’s symptomatic and sick. This is somebody for whom it might, logistically, take me some time to get that FISH result if it hasn’t been done, but you don’t want the patient sitting around while you’re doing that. What’s your approach? Is this someone you’d use more intensive treatment with and then scale back? Would you start with R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] and go up? How do you think about that generally? This is a very important practical thing for people.

Loretta Nastoupil, MD: Yeah, and it’s not as infrequent as I’d like it to be. Even here [The University of Texas MD Anderson Cancer Center], it takes a minimum of 7 days to get those FISH studies back. As you pointed out some of the key clinical characteristics, how concerned am I going to be that there are double-hit [lymphoma] features? I do look at the Ki-67, and when it’s 90% or higher, that’s worrisome. If they have underlying or concomitant, I know they already have 1 hit. My suspicion is going to be high that they’re going to have double-hit [lymphoma] features. Greg has reported on the time from diagnosis to the initiation of therapy: the sooner the better in terms of prognosis.

Generally, how quickly I need to initiate therapy to stabilize this patient is going to have an impact on how aggressive I will be. I don’t think there’s a downside to starting dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride], particularly in those patients who are high risk. Give them 1 cycle, and then you can de-escalate. The benefit of giving the slow-infusion doxorubicin during the first cycle is that you might reduce the risk for tumor lysis, because they oftentimes also have pretty substantial disease burden. I generally err on the side of be aggressive first and de-escalate, as opposed to trying to catch up with cycle 2.

John Leonard, MD: I agree with that. Any other comments? Anyone have a different view?

David Rizzieri, MD: No. John, could I pose this question to my colleagues? This has become a pet peeve of mine, and I torture my lymphoma colleagues here at Duke Healthf with it. What’s this a bridge to? You bring up double-hit lymphoma and the idea of escalating. We’re escalating toxicity, we’re escalating cost, and we’re escalating admissions to the hospital. I don’t know that we’re escalating benefit, and from a survival standpoint, all the phase 3 studies are negative, as Greg has pointed out, so unless we’re doing this as a bridge to something, I fail to see the need and impetus to continually escalate to more aggressive regimens, as you mentioned in the dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride]. What’s the goal?

John Leonard, MD: Anyone want to take a stab? There are 2 parts: 1, R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] is, in aggressive lymphomas or diffuse large B-cell lymphoma, generally trying to improve cure rates. But we haven’t done that. In the double-hit lymphoma group of patients, your point is well taken. It’s challenging to do a randomized trial. We’re actually working on that in Alliance using venetoclax with R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride], but the goal is pretty clear. The downside is there’s going to be more toxicity, and we’ve seen that, and the question is really going to be, “and we improve outcomes in the big picture? Until we do the studies, I don’t think we know the answer.

Loretta Nastoupil, MD: As those, a lot of those prospective randomized studies are going to be underrepresented with high-risk patients, because most of the time we make a clinical decision to start them on therapy. They can’t wait long enough to go on trial, so I don’t know that at least the cooperative group study really answers the question that R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] is as good as dose-adjusted R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride] for those high-risk patients.

David Rizzieri, MD: But all the phase 3 R-EPOCH [rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin hydrochloride] studies have been negative in any of the populations we’ve done it in. It’s tough for me to think that short of targeting, and I like the idea of targeting. As was mentioned, I think that’s going to be the real key, that we’re going to make real inroads here.

John Leonard, MD: Good point, good question.

TRANSCRIPT EDITED FOR CLARITY