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Hodgkin Lymphoma: Important Findings from CheckMate 205

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




Radhakrishnan Ramchandren, MD: Hodgkin lymphoma has demonstrated to be an exquisitely sensitive disease to immunotherapy. There are 2 approved checkpoint agents that have shown high clinical activity in this patient population. The tumors in Hodgkin lymphoma do express high levels of PD-L1 and PD-1, both in the tumor and the microenvironment, suggesting a possible target for checkpoint inhibitors. In addition, very elegant work done by Margaret Shipp and her lab has shown amplification and multiple copies of the gene for PD-L1 and PD-L2 on chromosome 9. This may be a potential source for overexpression, and may be a way to target patients and tumors in the future in checkpoint inhibitor therapy.

Stephen M. Ansell, MD, PhD: We’re looking at ways to improve the outcome of patients over standard therapy. So, a further approach has been to utilize a PD-1 blocking antibody, nivolumab, in combination with standard chemotherapy. The results with PD-1 blockade in relapsed patients have been very exciting. They show high response rates. Again, very durable. Now it’s being tested in the frontline setting.

Cohort D of the CheckMate-205 study looked at using nivolumab in combination with AVD chemotherapy. This was a small study of only 51 patients. It was more of a feasibility study, and it showed that you can safely combine nivolumab with AVD chemotherapy. It also had an interesting window to it where patients received nivolumab alone, first, for 2 months, and then received the combination. That gave us some insight into the efficacy of nivolumab as the frontline, first treatment. And it showed efficacy even as a single agent.
I think it’s going to take a randomized trial for us to really establish it as a frontline treatment option. At this point, it’s really still experimental and is still in its testing phase. So, I don’t think it actually impacts practice quite at this point. I think it’s something to be watching for in the future.

Radhakrishnan Ramchandren, MD: CheckMate-205 was a very important study because it looked at the use of nivolumab in Hodgkin lymphoma in a variety of clinical settings. Most importantly, in the first 3 cohorts of the study, it looked at nivolumab in the relapsed setting, either after brentuximab vedotin or after autologous stem cell transplant in a variety of ways. In those cohorts, a high response rate and, frankly, a very durable response rate was seen. In the last cohort, known as cohort D, nivolumab was evaluated in the frontline setting. This was the first ever instance where a checkpoint inhibitor was evaluated in the curative setting with chemotherapy. We learned a number of things. Importantly, I think we learned that nivolumab could be used in the frontline setting, and it is safe and tolerable. That is likely the primary take-home point from this.

Secondly, however, we evaluated and have a better understanding of the single-agent activity of nivolumab in this setting due to the lead-in period. Indeed, there was a response rate and a benefit seen in those patients who received nivolumab, even prior to receiving the combination of nivolumab and AVD. Lastly, we now have some appreciation for the response rate of this regimen, and curative potential, which you will learn as time goes on.

Transcript Edited for Clarity
 
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Radhakrishnan Ramchandren, MD: Hodgkin lymphoma has demonstrated to be an exquisitely sensitive disease to immunotherapy. There are 2 approved checkpoint agents that have shown high clinical activity in this patient population. The tumors in Hodgkin lymphoma do express high levels of PD-L1 and PD-1, both in the tumor and the microenvironment, suggesting a possible target for checkpoint inhibitors. In addition, very elegant work done by Margaret Shipp and her lab has shown amplification and multiple copies of the gene for PD-L1 and PD-L2 on chromosome 9. This may be a potential source for overexpression, and may be a way to target patients and tumors in the future in checkpoint inhibitor therapy.

Stephen M. Ansell, MD, PhD: We’re looking at ways to improve the outcome of patients over standard therapy. So, a further approach has been to utilize a PD-1 blocking antibody, nivolumab, in combination with standard chemotherapy. The results with PD-1 blockade in relapsed patients have been very exciting. They show high response rates. Again, very durable. Now it’s being tested in the frontline setting.

Cohort D of the CheckMate-205 study looked at using nivolumab in combination with AVD chemotherapy. This was a small study of only 51 patients. It was more of a feasibility study, and it showed that you can safely combine nivolumab with AVD chemotherapy. It also had an interesting window to it where patients received nivolumab alone, first, for 2 months, and then received the combination. That gave us some insight into the efficacy of nivolumab as the frontline, first treatment. And it showed efficacy even as a single agent.
I think it’s going to take a randomized trial for us to really establish it as a frontline treatment option. At this point, it’s really still experimental and is still in its testing phase. So, I don’t think it actually impacts practice quite at this point. I think it’s something to be watching for in the future.

Radhakrishnan Ramchandren, MD: CheckMate-205 was a very important study because it looked at the use of nivolumab in Hodgkin lymphoma in a variety of clinical settings. Most importantly, in the first 3 cohorts of the study, it looked at nivolumab in the relapsed setting, either after brentuximab vedotin or after autologous stem cell transplant in a variety of ways. In those cohorts, a high response rate and, frankly, a very durable response rate was seen. In the last cohort, known as cohort D, nivolumab was evaluated in the frontline setting. This was the first ever instance where a checkpoint inhibitor was evaluated in the curative setting with chemotherapy. We learned a number of things. Importantly, I think we learned that nivolumab could be used in the frontline setting, and it is safe and tolerable. That is likely the primary take-home point from this.

Secondly, however, we evaluated and have a better understanding of the single-agent activity of nivolumab in this setting due to the lead-in period. Indeed, there was a response rate and a benefit seen in those patients who received nivolumab, even prior to receiving the combination of nivolumab and AVD. Lastly, we now have some appreciation for the response rate of this regimen, and curative potential, which you will learn as time goes on.

Transcript Edited for Clarity
 
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