James Armitage: Hello, I’m Jim Armitage from the University of Nebraska Medical Center. I want to welcome you to The ASCO Post Video Roundtable Series featuring the Management of Challenging Cases of Patients With Myeloma and Lymphoma. This installment will highlight current treatment options for patients with relapsed/refractory diffuse large B-cell lymphoma, and though we did not forget CAR T-cell therapy, as discussed in a separate installment. Now today I am joined by two of my colleagues, and they will introduce themselves.
Matthew Lunning: Hi, I’m Matthew Lunning. I’m associate professor at the University of Nebraska Medical Center. I specialize in lymphoma and cellular therapy.
Sarah Holstein: Hi, I’m Sarah Holstein. I’m an associate professor at the University of Nebraska Medical Center, and I specialize in multiple myeloma and related plasma cell disorders.
Dr. Armitage: Okay, Matt. Are you going to handle all these? It’s a disease that has changed about as much as it is possible to change.
Dr. Armitage: Alright. Your patient is a 52-year-old man who found a neck mass himself, presented to his doctor, was given antibiotics, didn’t benefit, a biopsy was done, and a diagnosis was made of diffuse large B-cell lymphoma. It was a non-GCB double expresser. PET was positive in neck, mediastinum, axilla, and retroperitoneum. The maximum SUV was 29. A bone marrow biopsy was negative, and the LDH was slightly above normal. He receives six CHOP-Rs and achieved a post-treatment PET with a Deauville 2. Nine months later, he felt a new node in his neck. He comes back. He gets biopsied again. It is diffuse large B-cell lymphoma. The PET scan shows disease now just in the neck and mediastinum, and the maximum SUV is 18. How would you approach such a person?
Dr. Lunning: Well, I think that this is a situation that is concerning for large-cell lymphoma. Obviously when you are starting off with a diagnosis for diffuse large B-cell lymphoma, it’s curative intent, and you are upfront with them that you need to get all the staging tests done. And this patient had what sounds like appropriate staging tests performed and then received initial therapy with R-CHOP. I think R-CHOP is still the standard of care in patients with double-expressing large-cell lymphoma, and looking at their IPI score trying to go through the numbers, not knowing his performance status but assuming he had a good performance status, he had stage and elevated LVH I think, so, IPI score of 2, you know getting into a complete remission happens. It sounds like this person relapsed within a year, and so in that situation, that’s concerning to me. I mean, primary refractory disease, relapsing within a year is not good. So knowing that we have a biopsy confirming that this is still a diffuse large B-cell lymphoma, I think there are certain circumstances where you can do a biopsy and it comes back a different kind of lymphoma, an antecedent into lymphoma. In this case, you know given the immunophenotype. With a non-GCB, it would more likely be a marginal zone lymphoma or something like that. I think that this patient, I’m assuming that they’re a transplant-eligible patient, and so I would actually offer them rituximab followed by ICE.
We’ve done historically two cycles of ICE. I think that’s interesting because of a lot of centers do three cycles and mobilize off the third. I would give two cycles of RICE and then do a PET scan at the end of two cycles. That being said, we are in a very interesting point in the management of large-cell lymphoma right now. This person relapsing within a year of the end of their therapy or about a year from the start of their therapy has a poor prognosis, but there are at least three if not two that are still actively accruing trials looking at second-line therapy and a transplant versus CAR T-cell. Now I know that that’s not a topic for this installment, but I think would be a discussion that I would be having with them when I meet them. These are the cases that I get a phone call about, and I’ll offer to see tomorrow because these people are progressing. Large-cell lymphoma doesn’t know that it is Saturday or a holiday or that it is midnight. It’s growing and so you want to try and get these patients on to get a true representation of where second-line therapy followed by a transplant fits and where it doesn’t fit compared to CAR T-cell.
So, off of a protocol like that I would offer him second-line combination chemotherapy with an intent, if chemo-sensitive, to go to high-dose therapy and autologous stem-cell rescue. That being said, I think that PET scans after two or three cycles of second-line therapy, you have to go in knowing their disease history, and I believe talking to them about that this may not work. Odds are is that you’ve got about a 50/50 chance of being chemo-sensitive. Getting into a complete remission may be even more difficult. It can occur but if it doesn’t occur, then we really need to look at that PET scan again because I am not sure that people who have this characteristic that go into a partial remission should go to transplant. But again partial remission is difficult to define, and you need to sit down and look at what their delta SUVs are, what the size of the lymph nodes are and make sure they really meet PR criteria, and then is it that everything got better or is it everything went away and one thing was left around that’s a little bit above liver background, because in those situations, I will consider that chemo sensitive or what I call a very good PR, and take them to transplant with the intent to radiate after transplant, that solitary refractory or site that did not get as optimal of a response as you had wanted.
Dr. Armitage: There are some places, including one where you trained once upon a time, who sometimes want to give that radiotherapy in that setting before the high-dose therapy and transplant, although we more often, as you just implied, give it after. What are the advantages and disadvantages of that?
Dr. Lunning: I would have a discussion if I think that a site was amenable to pre-transplant radiation with the radiation oncologist at the time of recurrence. Very rarely do we get solitary recurrences, but we do. But a lot of times if you have that PET done and you see one area that’s not responding like the others and if it is in a low morbidity region of the body, then I would discuss sometimes hyperfractionated radiation in this situation, just plan on doing that before. But that takes the patient, the radiation oncologist, and a lot of logistical gymnastics to get that done, but it can be done. If not, then we just plan to do it after transplant.
Dr. Armitage: Does the presence of – well this patient was a double expresser or a double hit, or somebody who has a Ki67 that thinks it is Burkitt lymphoma almost 100%, change what you do?
Dr. Lunning: So I think the double expressers in my mind is best defined what the prognosis is at diagnosis, less so at relapse. I think their disease is defining themselves. This disease has defined itself, meaning that it came back within a year from the end of the therapy or about year from diagnosis. Double hit – it depends upon what they got with their first line of therapy. If they received dose-adjusted EPOCH-R and they were dose-adjusted appropriately during their front-line therapy for their double-hit lymphoma, then that is just as concerning, but I don’t know that we have an alternative than a randomized trial of second-line therapy and transplant versus CAR T or trying to go to second-line therapy in this situation. I think you just have to try, and if you get a good response, then you’re still going to transplant because I think that is where the best data lies.
Dr. Armitage: And patients with extraordinarily high proliferating tumors you treat like everybody else?
Dr. Lunning: Yes, I don’t know that I increase the intensity. Maybe I increase the interval that I am looking to make sure that they are responding? If you have a primary refractory high Ki67, high-risk double hit lymphoma, am I going to make sure that they’re responding after one cycle of second-line therapy? Because I’m already probably talking to them about CAR T cell and having to get through two lines of therapy. But I don’t know that I would decrease the intensity of therapy just to get to CAR T cell. I still want to give these patients a chance if they’re transplant eligible to get to transplant, because the data is concerning that these patients may not do well, but most patients you can get them to CR or PET CR. At least in single institution data, those patients may still derive benefit from transplant.
Dr. Armitage: Okay. Thank you very much. We’re happy to have you watching. I want you to stay tuned for more installments of The ASCO Post Video Roundtable Series exploring other disease sites, and you will find those on ascopost.com.