DR EVENS: This was a patient that I’d heard about, about 2 and a half, 3 years ago, as somewhat of initial “curbsided”, he is now 61. He was around 59 at the time of diagnosis with ALK-negative anaplastic large cell lymphoma who had presented with Stage IV disease, but interestingly had a fairly low tumor burden. His LDH was normal. His IPI was calculated at 2 altogether. And the decision was to treat him with CHOEP, in other words, CHOP plus etoposide. And we had talked about a consolidative autologous stem cell transplant. The patient had lived somewhat farther in the community, so he ended up receiving the 6 cycles, did go into a CR, ended up not proceeding with the autologous consolidative transplant.
Did fine, but about 12 months after finishing therapy — so about almost 18 months from the initial diagnosis — biopsy-proven relapse. Was in multiple areas above and below the diaphragm, not that symptomatic. He did experience some neuropathy sensory to the CHOEP therapy, wasn’t debilitating but probably was at least a Grade I already at baseline at this point. And then this is when I met him in consultation. So in summary, now 61-year-old relapsed/refractory, ALK-negative ALCL who had a fairly brief remission to CHOEP therapy.
DR LOVE: So Chris, what would you be thinking?
DR FLOWERS: So I think this is a younger individual who would still be a candidate for autologous stem cell transplantation. I definitely would bring that up as a potential option after an intensive chemotherapy regimen. We typically would use ICE as the chemotherapy regimen. Now, having had etoposide in his up-front therapy, I’d be a little less enthusiastic about that regimen, not knowing that the etoposide is the agent that I’m depending on most in that second-line therapy. But I would consider another regimen, like DAP or maybe a gemcitabine-based regimen like GDP as a second-line therapy, either with or without a transplant.
DR LOVE: Mike?
DR EVENS: And which type of transplant?
DR FLOWERS: So, that’s a great question. I think autologous transplant still needs to be in the discussion. I would also type siblings at that time and look to see what his allogeneic options are as well and have that discussion about the role of autologous transplant in relapse versus an allogeneic transplant.
Likewise, I think the other agents that we talked about, pralatrexate and romidepsin, would be other options, if you’re considering a less intensive approach.
DR EVENS: There’s one other.
DR LOVE: So Mike, what would you be thinking?
DR WILLIAMS: In this patient, we’d probably be looking at getting him into a remission with brentuximab and then moving toward an auto would be the approach. I agree, it’s reasonable to look for siblings and if he’s got that option, then I guess that’d be another discussion about whether to go to —
DR VOSE: I would definitely use brentuximab vedotin for salvage, very good response rates in that type of patient. And then go on to transplant. And the transplant option, autotransplant in a relapsed T-cell lymphoma is not very good. So we probably would try to look for an allo option, if that’s possible, and if the patient’s otherwise an appropriate candidate. But that doesn’t always happen. So then, as a second choice, we would still probably consider auto.
DR FRIEDBERG: Julie, what kind of outcomes would you suggest to that patient, if they had a sibling, 10 out of 10. How has your experience been with aggressive histology T cells in the allogeneic situation?
DR VOSE: So if they have a sibling donor and are in remission at the time of transplant, the data are actually not that bad. It’s probably 40 to 50%, 2- to 3-year disease-free survival and survival. There’s actually an abstract that we’re not going to talk about today that was at Lugano that looked at that. And they had pretty good outcomes for those patients. So I think that’s a consideration.
DR LOVE: So what happened?
DR EVENS: So Julie might not remember. I had actually asked her about this case 8 months ago. The good news is, it was very similar to what she just said. It didn’t change too much. No. But this was the first case that I really grappled, of using it, brentuximab vedotin, somewhat off label. In other words, the label is for relapsed/refractory not amenable to a transplant. And we said, “He has neuropathy, so maybe a transplant is not in his cards.” But when you looked at it at face value with an overall response rate over 80% and a CR rate approaching 60%, when we went back and tried to look at ICE data, I’m not sure ICE gets you that high of a combination chemotherapy agent. And so to me, this is one that’s probably going to quickly move to the front line. Obviously, there’s an ongoing randomized trial.
So now there was some pause and hesitation. He did have that neuropathy. And he did run into some issues and we had to dose modify after the second dose. But he went into a very quick CR. And at least discussions with colleagues at the time, it was if he achieves a quick CR, then lean more toward auto. If he has trouble, doesn’t get into CR, is not quick, lean toward allo. And we basically headed down that path and, thankfully, went into a CR.
We did give him an ICE to mobilize, so I chickened out and gave him 1 cycle of chemotherapy and did fine. And he’s about 6 months — maybe 5 months out from an autotransplant right now and in CR.
DR LOVE: Jon, any thoughts about this case and about the issue of B-vedotin in ALCL?
DR FRIEDBERG: Yes. A couple of thoughts that I had. First of all, the comment was made he had a brief remission to the CHOEP. I’m not sure that the 18 months is really so brief. I think that’s kind of what you expect. And that’s part of what the message is, I think, that Julie was trying to say, is that I think that for many oncologists, the concept is, “Even if the patient’s going to relapse, they’ll have a long time.” I think by 2 years, a lot of these patients do progress.
I agree that the autologous transplant studies have suggested, in the relapsed setting, that there are poor outcomes. I would say, with a little caveat, though, that that was when we were using chemotherapy as a bridge to the auto. And we don’t really know what it’s going to be like in this type of situation.
I think the clearer treatment choice is to give brentuximab vedotin to a patient like this. I think the question is then what to do after. We haven’t been doing a lot of allogeneic transplants in this situation, but we may need to revisit that based on some of the discussion today.