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Hodgkin Lymphoma: Upfront Brentuximab Vedotin + AVD

Panelists: John Leonard, MD, New York-Presbyterian/Weill Cornell Center for Lymphoma and Myeloma; C. Ola Landgren, MD, Memorial Sloan Kettering Cancer Center; Alexander Perl, MD, Perelman School of Medicine, University of Pennsylvania; Anas Younes, MD, Memorial Sloan Kettering Cancer Center
Published: Thursday, Dec 07, 2017



Transcript: 

John Leonard, MD: Welcome to this OncLive® News Network® presentation, broadcasting live from MJH Studios™. Today’s discussion will be focused on the latest advances in treating hematologic malignancies with a focus on lymphoma, leukemia, and multiple myeloma. I’m your host, Dr John Leonard, professor and associate dean at Weill Cornell Medical College and New York-Presbyterian Hospital. Today, I’m joined by 3 of my colleagues who are leading experts in their fields. I’ll have them introduce themselves.

C. Ola Landgren, MD: Thank you for having me, John. I’m Ola Landgren. I’m professor of medicine and chief of the Myeloma Service at Memorial Sloan-Kettering Cancer Center.

Alexander Perl, MD: I’m Alexander Perl. I’m a member of the leukemia program at the Abramson Cancer Center at the hospital of the University of Pennsylvania.

Anas Younes, MD: And I’m Anas Younes, chief of Lymphoma Service at Memorial Sloan-Kettering Cancer Center.

John Leonard, MD: Well, thank you all for joining us today. I’m really excited about our discussion. Over the next several minutes, we’re going to spend some time talking about the data that are going to be presented at the upcoming 2017 American Society of Hematology Annual Meeting [ASH]. We’re all getting ready to go. We’ve been looking through the abstracts in advance and we’re going to highlight the most important studies that are focusing on lymphoma, leukemia, and myeloma, and our goal here is really to provide you with perspective on how the data may shape the way that we treat our patients with these diseases. And then in the last few minutes of the broadcast, we’re going to answer questions that were submitted from the audience in advance. So, we’re going to work through each of our discussants and each of our topic areas.

We’re going to first start with lymphoma and Anas Younes. So, Anas, there’s a lot happening in Hodgkin lymphoma, which is where we’ll kick things off. We have a plenary session talk, a study you’ve been involved with, a drug you and many others have been involved with, and that’s the phase III study looking at up-front brentuximab vedotin as part of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in Hodgkin lymphoma. So, can you tell us a little bit about that?

Anas Younes, MD: Yes. Thanks, John. So, finally, we got the data that will be presented at the plenary session at ASH, which is a randomized phase III trial comparing standard ABVD with the experimental arm, which is brentuximab plus AVD, no bleomycin. More than 1300 patients were randomized. The primary endpoint is met with about 5% difference in PFS at 2 years, and then this is news for us for Hodgkin lymphoma.

John Leonard, MD: So, how do you think this is going to affect your practice seeing patients? Clearly, there is a progression-free survival benefit. There’s not an overall survival benefit in the data that we’ve seen. There’s a little more toxicity, at least in some ways. We have the variable of bleomycin in here now. How do you think the field is going to respond, patients are going to be treated, in your practice?

Anas Younes, MD: It’s a very good question. I think it’s going to be subjected to a lot of scrutiny based on subsets and analysis of patients who may have a higher benefit compared to others, so those who may get a benefit more than 5% and others who may not benefit that much. I think by face value, it’s progress regardless how you cut it. The field has been stable for more than 4 decades, so this is good news that we have something beyond ABVD. We would have liked it to be more positive than 5%, of course, but I think it provides an option to some patients. Whether this is going to be a blanket treatment or not, I don’t know, but I think it’s a good option for some patients.

John Leonard, MD: Because this is such an important, potentially practice-changing abstract, what would you say to the audience from the standpoint of looking at the data? What are you going to focus on from the standpoint of taking us back, and then the next patient you see, having that discussion? What’s going to be the key issue? Because I think this is really important for people to…

Anas Younes, MD: As I said, I think we have to wait and look at the data in more detail in the subsets and then make decisions. There’s now embargo on the data that we cannot discuss right now. But I can tell you that there are some subsets that benefited more than the average 5%, and I think this probably would be a good patient population to be offered this treatment strategy.

John Leonard, MD: Great. So, a couple of the other important abstracts that we wanted to talk about in Hodgkin’s also reference brentuximab vedotin. One of those is by Fornecker and colleagues, the European study, looking at the A + AVD, essentially plugging in brentuximab vedotin as part of ABVD, swapping in for bleomycin, and looking at a PET-based response after 2 cycles. So, your thoughts on that study? I think it was an interesting design.

Anas Younes, MD: Yes, it’s an interesting design. So, the question is, can we advance brentuximab vedotin to early-stage patients? This is more tricky because early-stage patients do very well, so it’s very difficult to find improvement beyond the 1992 percentage of progression-free survival with standard ABVD or plus/minus radiation therapy. So, the endpoint here was a PET-2 negative status, and it is about a 7% difference in PET-2 negative, particularly between the ABVD versus AVD plus brentuximab. I think it’s too early to call. We need to look at the curves and the long-term follow-up, not only just the PFS. We need to look if this is going to change the safety profile. I think most people will be interested in the frontline setting, whether the incorporation of brentuximab vedotin will make you less likely to need radiation therapy, and unfortunately, this trial did not look at the big question.

John Leonard, MD: Yes, I think that’s a key point that this trial, all patients had radiation. And so, how that figures into the mix if you’re leaving out radiation, which many of us obviously do, will be of interest. And then finally, we’re now getting into, in Hodgkin’s, the novel agents or biologic combinations. We have Alex Herrera and the group at City of Hope and others presenting data, phase I-II trial in relapsed Hodgkin patients—the pretransplant population for the most part—looking at brentuximab vedotin where we’ve seen a number of different studies trying to use that pretransplant in this case with nivolumab. So, where do you see those data?

Anas Younes, MD: Yes, and you will see that actually in multiple updates. So, this abstract has been presented multiple times in the past. This is mainly an update with more patients and more follow-ups. There are about 60 patients now treated with this combination in the pre-transplant setting. This is first qualifying salvage before transplant looking at response rate. Can we increase the CR rates so patients become more qualified for transplant? I think it’s very interesting because this is a chemotherapy-free regimen, just 2 drugs. So, when you get to transplant, you’re probably in better shape and not beaten up by chemotherapy. About 60% CR rate with about an 80% overall response rate is very impressive. As you know, this doublet now has been moved to randomized trials in the posttransplant setting, which is seeking approval. So, the randomized trial is this doublet, nivolumab plus brentuximab, compared to the standard brentuximab alone. This is an ongoing randomized trial.

Transcript Edited for Clarity 
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Transcript: 

John Leonard, MD: Welcome to this OncLive® News Network® presentation, broadcasting live from MJH Studios™. Today’s discussion will be focused on the latest advances in treating hematologic malignancies with a focus on lymphoma, leukemia, and multiple myeloma. I’m your host, Dr John Leonard, professor and associate dean at Weill Cornell Medical College and New York-Presbyterian Hospital. Today, I’m joined by 3 of my colleagues who are leading experts in their fields. I’ll have them introduce themselves.

C. Ola Landgren, MD: Thank you for having me, John. I’m Ola Landgren. I’m professor of medicine and chief of the Myeloma Service at Memorial Sloan-Kettering Cancer Center.

Alexander Perl, MD: I’m Alexander Perl. I’m a member of the leukemia program at the Abramson Cancer Center at the hospital of the University of Pennsylvania.

Anas Younes, MD: And I’m Anas Younes, chief of Lymphoma Service at Memorial Sloan-Kettering Cancer Center.

John Leonard, MD: Well, thank you all for joining us today. I’m really excited about our discussion. Over the next several minutes, we’re going to spend some time talking about the data that are going to be presented at the upcoming 2017 American Society of Hematology Annual Meeting [ASH]. We’re all getting ready to go. We’ve been looking through the abstracts in advance and we’re going to highlight the most important studies that are focusing on lymphoma, leukemia, and myeloma, and our goal here is really to provide you with perspective on how the data may shape the way that we treat our patients with these diseases. And then in the last few minutes of the broadcast, we’re going to answer questions that were submitted from the audience in advance. So, we’re going to work through each of our discussants and each of our topic areas.

We’re going to first start with lymphoma and Anas Younes. So, Anas, there’s a lot happening in Hodgkin lymphoma, which is where we’ll kick things off. We have a plenary session talk, a study you’ve been involved with, a drug you and many others have been involved with, and that’s the phase III study looking at up-front brentuximab vedotin as part of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in Hodgkin lymphoma. So, can you tell us a little bit about that?

Anas Younes, MD: Yes. Thanks, John. So, finally, we got the data that will be presented at the plenary session at ASH, which is a randomized phase III trial comparing standard ABVD with the experimental arm, which is brentuximab plus AVD, no bleomycin. More than 1300 patients were randomized. The primary endpoint is met with about 5% difference in PFS at 2 years, and then this is news for us for Hodgkin lymphoma.

John Leonard, MD: So, how do you think this is going to affect your practice seeing patients? Clearly, there is a progression-free survival benefit. There’s not an overall survival benefit in the data that we’ve seen. There’s a little more toxicity, at least in some ways. We have the variable of bleomycin in here now. How do you think the field is going to respond, patients are going to be treated, in your practice?

Anas Younes, MD: It’s a very good question. I think it’s going to be subjected to a lot of scrutiny based on subsets and analysis of patients who may have a higher benefit compared to others, so those who may get a benefit more than 5% and others who may not benefit that much. I think by face value, it’s progress regardless how you cut it. The field has been stable for more than 4 decades, so this is good news that we have something beyond ABVD. We would have liked it to be more positive than 5%, of course, but I think it provides an option to some patients. Whether this is going to be a blanket treatment or not, I don’t know, but I think it’s a good option for some patients.

John Leonard, MD: Because this is such an important, potentially practice-changing abstract, what would you say to the audience from the standpoint of looking at the data? What are you going to focus on from the standpoint of taking us back, and then the next patient you see, having that discussion? What’s going to be the key issue? Because I think this is really important for people to…

Anas Younes, MD: As I said, I think we have to wait and look at the data in more detail in the subsets and then make decisions. There’s now embargo on the data that we cannot discuss right now. But I can tell you that there are some subsets that benefited more than the average 5%, and I think this probably would be a good patient population to be offered this treatment strategy.

John Leonard, MD: Great. So, a couple of the other important abstracts that we wanted to talk about in Hodgkin’s also reference brentuximab vedotin. One of those is by Fornecker and colleagues, the European study, looking at the A + AVD, essentially plugging in brentuximab vedotin as part of ABVD, swapping in for bleomycin, and looking at a PET-based response after 2 cycles. So, your thoughts on that study? I think it was an interesting design.

Anas Younes, MD: Yes, it’s an interesting design. So, the question is, can we advance brentuximab vedotin to early-stage patients? This is more tricky because early-stage patients do very well, so it’s very difficult to find improvement beyond the 1992 percentage of progression-free survival with standard ABVD or plus/minus radiation therapy. So, the endpoint here was a PET-2 negative status, and it is about a 7% difference in PET-2 negative, particularly between the ABVD versus AVD plus brentuximab. I think it’s too early to call. We need to look at the curves and the long-term follow-up, not only just the PFS. We need to look if this is going to change the safety profile. I think most people will be interested in the frontline setting, whether the incorporation of brentuximab vedotin will make you less likely to need radiation therapy, and unfortunately, this trial did not look at the big question.

John Leonard, MD: Yes, I think that’s a key point that this trial, all patients had radiation. And so, how that figures into the mix if you’re leaving out radiation, which many of us obviously do, will be of interest. And then finally, we’re now getting into, in Hodgkin’s, the novel agents or biologic combinations. We have Alex Herrera and the group at City of Hope and others presenting data, phase I-II trial in relapsed Hodgkin patients—the pretransplant population for the most part—looking at brentuximab vedotin where we’ve seen a number of different studies trying to use that pretransplant in this case with nivolumab. So, where do you see those data?

Anas Younes, MD: Yes, and you will see that actually in multiple updates. So, this abstract has been presented multiple times in the past. This is mainly an update with more patients and more follow-ups. There are about 60 patients now treated with this combination in the pre-transplant setting. This is first qualifying salvage before transplant looking at response rate. Can we increase the CR rates so patients become more qualified for transplant? I think it’s very interesting because this is a chemotherapy-free regimen, just 2 drugs. So, when you get to transplant, you’re probably in better shape and not beaten up by chemotherapy. About 60% CR rate with about an 80% overall response rate is very impressive. As you know, this doublet now has been moved to randomized trials in the posttransplant setting, which is seeking approval. So, the randomized trial is this doublet, nivolumab plus brentuximab, compared to the standard brentuximab alone. This is an ongoing randomized trial.

Transcript Edited for Clarity 
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