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Relapsed/Refractory Hodgkin Lymphoma

This is Part 4 of Updates in Lymphoma, a four-part video roundtable series. Scroll down to watch the other videos from this Roundtable.

In this video, Drs. Alison J. Moskowitz, Andrew M. Evens, and Ann S. LaCasce discuss the management of relapsed/refractory Hodgkin lymphoma. The patient is a 36-year-old woman who was originally diagnosed with stage IIIB classical Hodgkin lymphoma with a 12-cm mediastinal mass and an IPS of 2. She received BV-AVD for 6 cycles, with a PET-negative response after two and six cycles of treatment. However, repeat PET scan showed new and increasing hypermetabolic masses in the anterior mediastinum. The faculty discuss treatment options for patients with primary refractory disease, including brentuximab vedotin plus nivolumab and pembrolizumab plus gemcitabine, vinorelbine, and doxorubicin.


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Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Dr. Alison Moskowitz: Welcome to The ASCO Post Roundtable Series on updates in lymphoma. I'm Dr. Alison Moskowitz, an Associate Attending from the lymphoma service at Memorial Sloan Kettering Cancer Center. Joining me are two of my colleagues who will introduce themselves. Dr. Ann LaCasce: I'm Dr. Ann LaCasce. I'm an Associate Professor at Dana-Farber Cancer Institute. Dr. Andy Evens: Hi, I'm Dr. Andy Evens, Associate Director of the Rutgers Cancer Institute of New Jersey. Dr. Moskowitz: Today, we will be discussing recent updates in Hodgkin lymphoma and integrating these new developments into four patient case studies. Our last installment will focus on relapse and refractory Hodgkin lymphoma. I will begin with a case. This is a 36-year-old woman who was originally diagnosed with stage IIIB classical Hodgkin lymphoma associated with a 12-centimeter mediastinal mass and an International Prognostic Score of 2. She received brentuximab plus AVD for six cycles. She had a PET-negative response after two and six cycles of treatment, but unfortunately, just one month after the completion of treatment, she developed her current pruritus, fatigue, shoulder pain, as well dullness in her chest. She underwent a repeat PET scan, which showed new and increasing hypermetabolic masses in the anterior mediastinum, with the largest mass measuring 5.6 centimeters with an SUV of 17.5. She had a biopsy of the dominant mediastinal mass that confirmed recurring classical Hodgkin lymphoma. I think I'll start with Ann. I'd love to hear your thoughts about how you initially approach a patient like this with primary refractory disease, or basically relapse very shortly after initial therapy. Dr. LaCasce: Well, fortunately from your data, looking at pembrolizumab combined with gemcitabine, vinorelbine, and Doxil, we now have a really good option. This patient's already had brentuximab upfront. Sometimes I will think about using brentuximab-nivolumab, but now that we have your data, which really looks quite remarkable in terms of both complete response rates and getting patients to transplant, that would clearly be what I would do in this setting. We have some good data, retrospective, mostly, that demonstrates giving a checkpoint inhibitor before stem cell transplant really does seem to result in better outcomes, somehow resensitizing patients to chemotherapy. So, I think now we're all really trying to incorporate these in the first-line relapse setting. And I think the question is, should all patients either get BV-nivo or pembro plus GVD? Or should anybody get ICE chemotherapy? And I think if someone had a contraindication to a checkpoint inhibitor because of an autoimmune disease or some other reason, then I might use ICE, or in a very late relapser. But I think this is a very appealing approach. And in a patient like this after auto-transplant, I would probably incorporate some radiation because this patient did have bulky chest disease, and I think we try to omit the radiation up front in as many patients as we can. And although this patient had stage III disease, she really did have quite bulky mediastinal disease, so I would radiate to really try to keep her in long-term remission. Dr. Moskowitz: Andy, anything to add to that or any other approaches? Dr. Evens: Yeah, no, I completely agree. This patient is previously obviously treated with brentuximab vedotin. There are still, of course, some patients who have not received BV in the upfront setting. Actually, Ann's regimen of BV-bendamustine was one I was using a lot before your regimen, Alison. So I'm often picking and choosing if someone had received straight ABVD between those two regimens. But they're both remarkably active, whether it's BV chemotherapy or in your regimen, the pembro-GVD. And so I think that's one point. The second is, do we need any chemotherapy? Could it be novel therapeutics? And so, of course, that partly depends on the upfront regimen. But I think the other, obviously, as these are bridges to autologous stem cell transplant, I guess the other question that's come up, I know you guys, Alison, at MSK are looking at, do all relapse Hodgkin's need an autologous stem cell transplant? Certainly a case like this that was presented, the answer would be, yes. It was a really primary refractory case. But maybe if there's some really late relapsers multiple years out, that could be a consideration, at least on a clinical trial. Dr. Moskowitz: Yeah. Just to expand on that a little bit. We do have two different clinical trials where we're looking at non-transplant approaches for patients, and actually, one of them is really for patients that kind of like what you described, someone who we would think of as really a favorable relapse patient. They can have primary refractory disease, but they have to have early-stage at initial diagnosis, they can't have bulky disease, and they have to relapse also with non-bulky early-stage disease and be eligible for radiation. And for those patients, we're looking to see if we can get away with just four cycles of pembrolizumab and radiation therapy as part of a clinical trial. And it's kind of tempting for a patient like that, to see if we can get away with such a little amount. For all the other patients, actually, even primary refractory, even patients with bulky, they are eligible for our other study where we're using pembro-GVD for four cycles, and those who have a complete response go onto pembrolizumab maintenance rather than transplant. I would never do this outside of a clinical trial and there's a lot of discussion that we have with patients with regard to informing them that this is outside of what our standard of care is since transplant is the standard of care. But we are looking to see if everyone needs this. And hopefully we'll learn that we can identify patients who don't need transplant. Or, also, one question I have is, are we going to find that a certain portion of patients can get away without transplant in the second-line setting, and that it's still effective in third-line for those who need it? And that's when we can then reintroduce our older regimens such as ICE and transplant. So, that's some of the things that we're looking at. But I 100% agree that our standard of care is to use a second-line therapy followed by transplant. I'm curious, Ann, for a patient who does not have a complete response to their initial salvage, what has been your approach in that setting? Dr. LaCasce: If someone had ICE, then I would try to incorporate a checkpoint inhibitor, either BV-nivo if they've not had BV or to use your pembro-GVD regimen. If patients have already had all those options and they have localized disease, I'll often radiate them before transplant. We've had good luck. We used to do that back in the day before we had all these novel agents. There certainly is a proportion of patients, I think, particularly with limited-stage disease who may do well with that approach. You get a lot more mucositis at transplant, so we use palifermin in those patients. I think that makes a big difference. But I think your point is well-taken. For patients who have disease that's in a radiation field, I think that's a very appealing group to think about omitting transplant. I think as I'm treating a lot of patients who've relapsed after auto right now, you do this long enough and you have a cohort of those patients, I'm a little bit nervous about omitting an auto, but it'll be really interesting to see if we can select those, particularly the late relapsers, the localized relapsers, elderly patients, who really don't need the auto. Dr. Moskowitz: Andy, are, are you using maintenance therapy after transplant for patients with relapse-refractory disease? Dr. Evens: Yeah, I was just going to dovetail on onto Ann's comment. So, maybe that would be a patient I would definitely think about it. In other words, one who did not achieve a CR to the salvage therapy. And I of course reflect back to your former colleague, Dr. Craig Moskowitz's data as he had published in the AETHERA study initially in Lancet and then follow up presentation at ISHL and in Blood showing that, for certain patients, and we know there are risk factors when you look at those, and this patient would be prime candidate for that study, meaning primary refractory or relapse within 12 months, PR SD as the best response, two prior therapies, extra-nodal disease, or B symptoms. And so, you needed any of those, but when you really look at deeper into the subsequent analysis with two or more of those risk factors, that absolute benefit was about 30%. In other words, a hazard ratio of 0.42, so a 60% improvement in progression-free survival. So those are patients I'm thinking about maintenance. Now, with that said this patient, I would not think about AETHERA because they had already received brentuximab vedotin, but there's some really interesting and excellent data that's been published with checkpoint inhibitor data use post-transplant in terms of maintenance, Alex Herrera, and others have published that. So I would think about that in a patient such as this case that you presented. Dr. Moskowitz: Great. Well, I think I will wrap up this case. So, as we all mentioned the standard approach for a patient with relapsed or refractory disease is to receive some kind of second-line therapy followed by consolidation with high-dose therapy and autologous stem transplant. There are multiple second-line therapies available. I have to say, I have also been impressed by the activity with pembro-GVD, and that has become my go-to regimen in the second-line setting. We've seen very high complete response rates and able to bridge most patients to transplant in that way. And so, in general, I am going to second-line therapies with PD-1 blockade and/or with brentuximab, given the high complete response rates, and considering maintenance therapy with brentuximab, or now with newer data showing activity with checkpoint inhibitors, should certainly be considered for higher risk patients. That brings us to the end of this case. Please see other segments for further discussion about the latest data in Hodgkin lymphoma or visit ascopost.com.
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