Optimization of PET Scans and Determining Relapse in DLBCL


Andre Goy, MD, MS: Dr Martin, when do you think is the best time to do a PET [positron emission tomography] scan? Interim PET scan, not post-treatment.

Peter Martin, MD: It’s a good question, and I think a lot of different institutions have done it differently over time. The standard at Weill Cornell Medicine, and I would bet at most institutions now, is after cycle 2. There was recently a study that we will see presented that tried to come out with a more evidence-based answer to this question, where a group of radiologists looked at a database of PET scan that were done after cycles 1, 2, 3, or 4, and found effectively that the best time to catch patients with the best response was a PET scan after cycle 2. Those PET scans had a very high negative predictive value.

Andre Goy, MD, MS: Regardless of the presentation, obviously.

Peter Martin, MD: Right. The best time to look at a patient who was likely to do poorly was a PET scan done after cycle 4. In practice that’s intuitive, I think that many of us are doing PET scans after cycle 2, and we feel good about ourselves when it looks good. If it looks a little bit less good but still appears to be on the right track, often I will give another couple of cycles and repeat the PET scan. If that’s positive then I’m a little bit more discouraged or am more likely to change therapy. I think that practice is probably pretty common and is supported by now a large database.

Andre Goy, MD, MS: I think for our audience it might be interesting to mention the fact that sometimes there is a “gray zone” PET scan interpretation, it’s better, but we still have some issues sometimes, particularly the interim PET scan. And then the delta issue, the drop of 60%, 70% really has an impact. It’s something that can be helpful. But I think want to switch to Nathan and say the PET scan always answers a lot of questions. No question, getting a negative PET scan post treatment is good. But I think there’s something that might be promising in the future, cell-free DNA, looking at cell-free DNA to quantify a response, and the combination of PET scan and cell-free DNA is extremely powerfully in some studies. Do you want to comment?

Nathan H. Fowler, MD: This is the big issue, being able to figure out, and I think it’s what we touched on with the IPI [International Prognostic Index] as well as PET scans. It’s at least been very difficult to not only figure out who is going to do poorly following induction therapy, but then trying to figure out when patients will relapse. What we’ve done in the past is do IPIs and PET scans and then do serial PET scans for a certain amount of time, and then move to long-term surveillance. There’s not a lot of evidence to do it this way to do it this way versus some other way. In other words, the scheduling for imaging is really based upon the patient’s risk for relapse.

I think the holy grail would be to develop some way that we could actually measure the disease at a molecular level and predict patients’ relapse before it happened clinically. This is the hope of determining or following patients’ cell-free DNA.

There have been several folks, actually this is something I think we’ve been doing now, my goodness, for about 7 years in different clinical trials. It’s yet to make it in the clinical practice but there are now commercial companies that are able to monitor cell-free DNA. In the large cell lymphoma trials, it looks very predictive. In fact, for most patients, they could predict relapse before you could pick it up on imaging studies.

Andre Goy, MD, MS: And they turn negative pretty quickly.

Nathan H. Fowler, MD: Yes. The other big thing, as you mentioned, is that not only could you potentially predict early relapses, but you can hopefully determine who could be cured. In patients who have a negative PET, we know that about 30% of those patients will still relapse. It will be ideal to be able to look at cell-free DNA in those negative PET scans and determine who would potentially need, for example, consolidation with the transplant.

Andre Goy, MD, MS: We talked about treatment, we talked about response on treatments. One of the questions that comes in lymphoma is maintenance therapy. Because there are still some patients who relapse, Dr Chavez, do you think there’s a role for maintenance therapy in large cell lymphoma?

Julio Chavez, MD: Yes, there have been several trials looking at maintenance therapy based on experience in the benefit of maintenance therapy in follicular lymphoma and mantle cell lymphoma. So, investigators thought that could be also applicable in diffuse large cell lymphoma. Unfortunately, there are no data so far that it improves survival. There are data following CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone]-based therapy in older patients with lenalidomide, even though there was a progression-free survival benefit, not really an overall survival benefit. So, we have to be very careful doing maintenance therapy when there aren’t strong data behind it, because it adds toxicity, and it may add cost to the patient and no real benefit.

At this time, I wouldn’t recommend maintenance therapy, post-frontline therapy for diffuse large cell lymphoma.

Andre Goy, MD, MS: The only maintenance benefit was actually the original ECOG [Eastern Cooperative Oncology Group] study when you have CHOP versus R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], the patient who had not received the R-CHOP had a benefit for the maintenance. But that was expected.

Grzegorz S. Nowakowski, MD: But they did not receive the R-CHOP.

Andre Goy, MD, MS: That was expected, yes. There is some discussion, not gender bias, but sex differences of kinetics of rituximab, where in France, they had a study where they looked at maintenance in males that showed maybe some benefit.

Transcript Edited for Clarity

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