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Novel Combinations in Relapsed Hodgkin Lymphoma

Insights From: Stephen M. Ansell, MD, PhD, Mayo Clinic; Radhakrishnan Ramchandren, MD, Wayne State University School of Medicine
Published: Friday, Jan 26, 2018



Stephen M. Ansell, MD, PhD: Two new agents that have been exciting news in Hodgkin lymphoma are brentuximab vedotin (BV) and PD-1 antibodies, either nivolumab or pembrolizumab. In this trial, the combination of brentuximab vedotin and nivolumab was given as the first treatment if patients had disease recurrence. It was used as a treatment to get patients back into remission. Then, there were considerations for proceeding to an autologous stem cell transplant.

It was not quite chemotherapy-free, but there was certainly very little in the way of chemotherapy, relatively speaking, because it’s only the drug that’s administered as part of the antibody drug conjugate, not typical chemotherapy. Again, the exciting part of this combination was that it was well tolerated. I think we were still learning as to whether we could combine these 2 agents, and that was quite successfully done. Secondly, the response rate was high, and the number of patients that were able to go on to transplant was also high.

A further question was, would this combination compromise the transplant process in any way? The study showed that this was not true and that patients could go on, collect stem cells, and proceed to transplant without any undue difficulty. So, I think the message from this trial is, this combination is very promising as a first salvage treatment.

Radhakrishnan Ramchandren, MD: As you know, there is no singular regimen that’s used universally for relapsed Hodgkin lymphoma. There are a variety of regimens—historically, chemotherapy based—that have been utilized. In patients who relapse after ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine], particularly those who have short relapses, salvage chemotherapy regimens have been less successful. So, utilizing novel agents in this population is a very important and clinically interesting question.

This was the first study that evaluated this clinically. This combined brentuximab vedotin and nivolumab for 4 cycles, prior to autologous stem cell transplant. In the salvage setting, the aim with relapsed Hodgkin lymphoma remains—and should remain—cure. So, it’s important, in this study, that we try to maintain the curative potential. Therefore, autologous stem cell transplant was included and mandated as part of the study.

The overall response rates and the complete response rates compare very well to salvage regimens that are used in Hodgkin lymphoma. From a toxicity profile, the BV/nivolumab regimen also appears to be favorable. That, in part, is due to the fact that many of the side effects that are associated with both brentuximab vedotin and nivolumab have been cumulative—particularly, neuropathy. A truncated course may minimize some of those adverse events. What we don’t know and what needs to be analyzed moving forward are the outcomes posttransplant in this population—whether novel therapy results in long-term disease-free survival similar to conventional chemotherapy needs to be ensured, so that we establish and maintain curative potential in the population.

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Stephen M. Ansell, MD, PhD: Two new agents that have been exciting news in Hodgkin lymphoma are brentuximab vedotin (BV) and PD-1 antibodies, either nivolumab or pembrolizumab. In this trial, the combination of brentuximab vedotin and nivolumab was given as the first treatment if patients had disease recurrence. It was used as a treatment to get patients back into remission. Then, there were considerations for proceeding to an autologous stem cell transplant.

It was not quite chemotherapy-free, but there was certainly very little in the way of chemotherapy, relatively speaking, because it’s only the drug that’s administered as part of the antibody drug conjugate, not typical chemotherapy. Again, the exciting part of this combination was that it was well tolerated. I think we were still learning as to whether we could combine these 2 agents, and that was quite successfully done. Secondly, the response rate was high, and the number of patients that were able to go on to transplant was also high.

A further question was, would this combination compromise the transplant process in any way? The study showed that this was not true and that patients could go on, collect stem cells, and proceed to transplant without any undue difficulty. So, I think the message from this trial is, this combination is very promising as a first salvage treatment.

Radhakrishnan Ramchandren, MD: As you know, there is no singular regimen that’s used universally for relapsed Hodgkin lymphoma. There are a variety of regimens—historically, chemotherapy based—that have been utilized. In patients who relapse after ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine], particularly those who have short relapses, salvage chemotherapy regimens have been less successful. So, utilizing novel agents in this population is a very important and clinically interesting question.

This was the first study that evaluated this clinically. This combined brentuximab vedotin and nivolumab for 4 cycles, prior to autologous stem cell transplant. In the salvage setting, the aim with relapsed Hodgkin lymphoma remains—and should remain—cure. So, it’s important, in this study, that we try to maintain the curative potential. Therefore, autologous stem cell transplant was included and mandated as part of the study.

The overall response rates and the complete response rates compare very well to salvage regimens that are used in Hodgkin lymphoma. From a toxicity profile, the BV/nivolumab regimen also appears to be favorable. That, in part, is due to the fact that many of the side effects that are associated with both brentuximab vedotin and nivolumab have been cumulative—particularly, neuropathy. A truncated course may minimize some of those adverse events. What we don’t know and what needs to be analyzed moving forward are the outcomes posttransplant in this population—whether novel therapy results in long-term disease-free survival similar to conventional chemotherapy needs to be ensured, so that we establish and maintain curative potential in the population.

Transcript Edited for Clarity
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