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New Study Finds Immunotherapy Effective in Treating Hodgkin Lymphoma
In this episode of the Better Edge Podcast, Jane Winter, MD, professor of Medicine in the Division of Hematology and Oncology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, discusses results from recent study published in the journal Blood. Findings showed that a brief course of immunotherapy resulted in complete and near complete remission in nearly two-thirds of previously untreated patients with classical Hodgkin lymphoma.
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Learn more about Jane Winter, MD
Jane Winter Begins Term as American Society of Hematology President-Elect
Jane Winter, MD
Jane Winter, MD is a Professor of Medicine Division of Hematology-Oncology.Learn more about Jane Winter, MD
Jane Winter Begins Term as American Society of Hematology President-Elect
Transcription:
New Study Finds Immunotherapy Effective in Treating Hodgkin Lymphoma
Melanie Cole: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and joining me today is Dr. Jane Winter. She's a Professor of Medicine in the Division of Hematology- Oncology, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and president elect of the American Society of Hematology.
She's joining me today to discuss Hodgkin lymphoma patients experiencing remission after immunotherapy and how findings from a recent study could impact treatment. Dr. Winter, it's a pleasure to have you join us today. Can you start by telling us a little bit about yourself and your area of expertise?
Dr. Jane Winter: I am a hematologist foremost. I specialize in hematologic malignancy, particularly lymphoproliferative, um, disorders. That means all of lymphomas, both Hodgkin's and non-Hodgkin's lymphoma. I'm trained also as an oncologist and I have focused in my career on diffuse large B-cell lymphoma, specifically prognostic markers, and in, um, development of novel therapeutics for all kinds of lymphomas, um, and more specifically lately, um, in Hodgkin's lymphoma,
Melanie Cole: Dr. Winter, have you seen an uptick of Hodgkin lymphoma patients experiencing remission after immunotherapy? You recently published a study in the Journal of Blood. Can you tell us about that study and its results?
Dr. Jane Winter: So this is a, um, unique study. The first time that, um, the checkpoint inhibitor, pembrolizumab, which is extensively used in solid tumors was used in the frontline treatment for Hodgkin's lymphoma. Um, we had observed, um, others in large clinical trials, um, the effectiveness of checkpoint inhibition in patients with relapsed disease, um, including patients who had failed, uh, numerous therapies, including stem cell transplant. And treatment with pembrolizumab or nivolumab, another checkpoint inhibitor, um, had proved very effective, but complete remission rates were not very high and patients invariably, or most patients at least, would relapse over time or progress. Um, our thoughts were that this very, um, effective therapy might be even more effective in previously untreated patients with a much more robust immune system.
So we hypothesized that pembrolizumab, uh, used in previously untreated patients would double the remission rates that had been seen in relapsed patients. So our study design was to administer, uh, a very brief course, just three treatments with pembrolizumab and to check a PET scan at that point to see how effective treatment had been.
Um, at that point, we then proceeded to what would be near standard therapy. A standard therapy would be ABVD chemotherapy, a four-drug cocktail they've been used for many years in Hodgkin's lymphoma. Uh, but we omitted the bleomycin, the B, because of concerns that there'd be an interaction, um, or increased numbers of pulmonary toxicities seen.
Patients got two cycles of the AVD and then we did another PET scan. The idea being to determine what the complete response rate might be at that point. In general, an early PET, a PET after two cycles of standard therapy is used to direct future treatment. Patients who have a positive PET scan at that point will generally transition to an alternative regimen, often escalated BEACOPP, a more aggressive regimen, and possibly radiotherapy. Patients who have a negative PET scan generally will go on to complete therapy with standard ABVD chemotherapy.
So we gave two cycles of AVD, checked a PET scan. And if they had a positive PET, we recommended that they go on to a more aggressive strategy. If they had a negative PET, they were to go on to standard AVD to continue either four or six cycles. We enrolled patients of all adult patients, um, including older patients. We had four patients over 65. Um, and these were patients, uh, with what we consider to be early unfavorable disease or advanced stage Hodgkin lymphoma.
We also in addition to doing PET scans, we evaluated how total metabolic volume, a measure of disease bulk, impacted treatment. So we enrolled 30 patients and the number of patients and the study design and statistics were to a large part determined by the amount of funding available, so only 30 patients. Uh, clearly, we would have liked to have enrolled more.
After three cycles of pembrolizumab, we had 11 of 30 patients achieve a complete metabolic response. Now, these included patients with very bulky diseases. Some of the patients had mediastinal masses that were as large as a volleyball, um, that, in the course of only three cycles of treatment, had completely disappeared.
We also noted that a significant number of additional patients had what we called a near complete metabolic response. These patients had greater than 90% resolution of their disease when we used this computer tool to assess the decline in treatment, that's the total metabolic volume. And my colleague, Dr. Hatice Savas, the radiologist who did those assessments-- and this was all central review, so this a multi-institution trial. We accrued the majority of the patients at Northwestern, 23 of 30, but we also enrolled patients at Emory; Pam Allen, who was the initially the fellow who wrote the trial with me and has authored the manuscript, she's the first author; as well as Dr. Andy Evans at Rutgers and Dr. Ranjana Advani at Stanford also enrolled patients. But we did review all of the PET scans centrally at Northwestern.
Um, so altogether we had nearly two-thirds of all patients in a complete or near complete metabolic response after three doses of pembro, so two-thirds, nearly 66%. We then went on to give all patients two cycles of AVD. And at the completion of those two cycles, all patients were in a complete metabolic response. No patient required a change of therapy. We went on to complete either four or six total cycles of AVD depending upon the patient's state.
Melanie Cole: And doctor, this is absolutely fascinating. And thank you for telling us what makes patients with Hodgkin lymphoma really good candidates for immunotherapy. So tell us about the long-term impact that this treatment could provide for patients and what are the next steps and future directions of this work? Where do you see it going from here?
Dr. Jane Winter: We are very impressed by this response. They allowed us to shorten the course of therapy, eliminate radiotherapy, especially for those with bulky disease, as well as to eliminate bleomycin. We feel that this is the first step to move us along towards eliminating or at least reducing the amount of therapy for patients. It's notable that not a single patient required an escalation to a more aggressive regimen or radiotherapy.
In terms of the future directions, there will soon be an international trial to confirm these findings. So we're very excited about that, and hope that ultimately, we will see the elimination of radiotherapy, bleomycin and possibly, at some point in the future, the elimination of the need for a chemotherapy.
Melanie Cole: Isn't that amazing? So tell us how your role in professional organizations like the American Society of Hematology advance that research that you're doing and contribute to shaping national guidelines for the treatment of blood cancers.
Dr. Jane Winter: So the American Society of Hematology is heavily, um, committed to raising the standard of care for patients around the world. And part of that is through support, um, at the national level for funding for clinical trials, cooperative groups, research through the NIH. We also are heavily committed to guidelines. For the most part at the present time, the ASH supported guidelines have been for non-malignant topics with the exception of acute myeloid leukemia.
Through the National Comprehensive Cancer Network, I've been involved in the development of guidelines for Hodgkin's lymphoma for more than two decades, I believe. So both organizations, NCCN, which has broad guidelines for every malignant disease including Hodgkin's, all the lymphomas, as well as the American Society of Hematology, sometimes in partnership with other organizations, are really establishing important, um, tools and guides for the practicing physician.
Melanie Cole: As we wrap up, what else would you like providers to know to take forward to optimize patient outcomes and how the results from your study can change treatment protocols for these types of cancers?
Dr. Jane Winter: I think perhaps the most important thing is to consider involvement in clinical trials. Every single new advance is based on data from clinical trials. Today, more than ever, uh, many new drugs for the blood cancers have been approved by the FDA in the past few years than ever before. So it's a very exciting time, but every one of those new approvals is based on clinical trial data. So participation is key. And in the US, we do a very poor job of enrolling patients in clinical trials compared to our counterparts in Europe where a large proportion of patients participate in clinical trials and they're able to complete large clinical trials very quickly. So we need to do better.
Melanie Cole: Thank you so much, Dr. Winter. What a very interesting episode this was. Thank you again for joining us. And to refer your patient, please visit our website at nm.org/cancer to get connected with one of our providers.
That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.
New Study Finds Immunotherapy Effective in Treating Hodgkin Lymphoma
Melanie Cole: Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and joining me today is Dr. Jane Winter. She's a Professor of Medicine in the Division of Hematology- Oncology, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and president elect of the American Society of Hematology.
She's joining me today to discuss Hodgkin lymphoma patients experiencing remission after immunotherapy and how findings from a recent study could impact treatment. Dr. Winter, it's a pleasure to have you join us today. Can you start by telling us a little bit about yourself and your area of expertise?
Dr. Jane Winter: I am a hematologist foremost. I specialize in hematologic malignancy, particularly lymphoproliferative, um, disorders. That means all of lymphomas, both Hodgkin's and non-Hodgkin's lymphoma. I'm trained also as an oncologist and I have focused in my career on diffuse large B-cell lymphoma, specifically prognostic markers, and in, um, development of novel therapeutics for all kinds of lymphomas, um, and more specifically lately, um, in Hodgkin's lymphoma,
Melanie Cole: Dr. Winter, have you seen an uptick of Hodgkin lymphoma patients experiencing remission after immunotherapy? You recently published a study in the Journal of Blood. Can you tell us about that study and its results?
Dr. Jane Winter: So this is a, um, unique study. The first time that, um, the checkpoint inhibitor, pembrolizumab, which is extensively used in solid tumors was used in the frontline treatment for Hodgkin's lymphoma. Um, we had observed, um, others in large clinical trials, um, the effectiveness of checkpoint inhibition in patients with relapsed disease, um, including patients who had failed, uh, numerous therapies, including stem cell transplant. And treatment with pembrolizumab or nivolumab, another checkpoint inhibitor, um, had proved very effective, but complete remission rates were not very high and patients invariably, or most patients at least, would relapse over time or progress. Um, our thoughts were that this very, um, effective therapy might be even more effective in previously untreated patients with a much more robust immune system.
So we hypothesized that pembrolizumab, uh, used in previously untreated patients would double the remission rates that had been seen in relapsed patients. So our study design was to administer, uh, a very brief course, just three treatments with pembrolizumab and to check a PET scan at that point to see how effective treatment had been.
Um, at that point, we then proceeded to what would be near standard therapy. A standard therapy would be ABVD chemotherapy, a four-drug cocktail they've been used for many years in Hodgkin's lymphoma. Uh, but we omitted the bleomycin, the B, because of concerns that there'd be an interaction, um, or increased numbers of pulmonary toxicities seen.
Patients got two cycles of the AVD and then we did another PET scan. The idea being to determine what the complete response rate might be at that point. In general, an early PET, a PET after two cycles of standard therapy is used to direct future treatment. Patients who have a positive PET scan at that point will generally transition to an alternative regimen, often escalated BEACOPP, a more aggressive regimen, and possibly radiotherapy. Patients who have a negative PET scan generally will go on to complete therapy with standard ABVD chemotherapy.
So we gave two cycles of AVD, checked a PET scan. And if they had a positive PET, we recommended that they go on to a more aggressive strategy. If they had a negative PET, they were to go on to standard AVD to continue either four or six cycles. We enrolled patients of all adult patients, um, including older patients. We had four patients over 65. Um, and these were patients, uh, with what we consider to be early unfavorable disease or advanced stage Hodgkin lymphoma.
We also in addition to doing PET scans, we evaluated how total metabolic volume, a measure of disease bulk, impacted treatment. So we enrolled 30 patients and the number of patients and the study design and statistics were to a large part determined by the amount of funding available, so only 30 patients. Uh, clearly, we would have liked to have enrolled more.
After three cycles of pembrolizumab, we had 11 of 30 patients achieve a complete metabolic response. Now, these included patients with very bulky diseases. Some of the patients had mediastinal masses that were as large as a volleyball, um, that, in the course of only three cycles of treatment, had completely disappeared.
We also noted that a significant number of additional patients had what we called a near complete metabolic response. These patients had greater than 90% resolution of their disease when we used this computer tool to assess the decline in treatment, that's the total metabolic volume. And my colleague, Dr. Hatice Savas, the radiologist who did those assessments-- and this was all central review, so this a multi-institution trial. We accrued the majority of the patients at Northwestern, 23 of 30, but we also enrolled patients at Emory; Pam Allen, who was the initially the fellow who wrote the trial with me and has authored the manuscript, she's the first author; as well as Dr. Andy Evans at Rutgers and Dr. Ranjana Advani at Stanford also enrolled patients. But we did review all of the PET scans centrally at Northwestern.
Um, so altogether we had nearly two-thirds of all patients in a complete or near complete metabolic response after three doses of pembro, so two-thirds, nearly 66%. We then went on to give all patients two cycles of AVD. And at the completion of those two cycles, all patients were in a complete metabolic response. No patient required a change of therapy. We went on to complete either four or six total cycles of AVD depending upon the patient's state.
Melanie Cole: And doctor, this is absolutely fascinating. And thank you for telling us what makes patients with Hodgkin lymphoma really good candidates for immunotherapy. So tell us about the long-term impact that this treatment could provide for patients and what are the next steps and future directions of this work? Where do you see it going from here?
Dr. Jane Winter: We are very impressed by this response. They allowed us to shorten the course of therapy, eliminate radiotherapy, especially for those with bulky disease, as well as to eliminate bleomycin. We feel that this is the first step to move us along towards eliminating or at least reducing the amount of therapy for patients. It's notable that not a single patient required an escalation to a more aggressive regimen or radiotherapy.
In terms of the future directions, there will soon be an international trial to confirm these findings. So we're very excited about that, and hope that ultimately, we will see the elimination of radiotherapy, bleomycin and possibly, at some point in the future, the elimination of the need for a chemotherapy.
Melanie Cole: Isn't that amazing? So tell us how your role in professional organizations like the American Society of Hematology advance that research that you're doing and contribute to shaping national guidelines for the treatment of blood cancers.
Dr. Jane Winter: So the American Society of Hematology is heavily, um, committed to raising the standard of care for patients around the world. And part of that is through support, um, at the national level for funding for clinical trials, cooperative groups, research through the NIH. We also are heavily committed to guidelines. For the most part at the present time, the ASH supported guidelines have been for non-malignant topics with the exception of acute myeloid leukemia.
Through the National Comprehensive Cancer Network, I've been involved in the development of guidelines for Hodgkin's lymphoma for more than two decades, I believe. So both organizations, NCCN, which has broad guidelines for every malignant disease including Hodgkin's, all the lymphomas, as well as the American Society of Hematology, sometimes in partnership with other organizations, are really establishing important, um, tools and guides for the practicing physician.
Melanie Cole: As we wrap up, what else would you like providers to know to take forward to optimize patient outcomes and how the results from your study can change treatment protocols for these types of cancers?
Dr. Jane Winter: I think perhaps the most important thing is to consider involvement in clinical trials. Every single new advance is based on data from clinical trials. Today, more than ever, uh, many new drugs for the blood cancers have been approved by the FDA in the past few years than ever before. So it's a very exciting time, but every one of those new approvals is based on clinical trial data. So participation is key. And in the US, we do a very poor job of enrolling patients in clinical trials compared to our counterparts in Europe where a large proportion of patients participate in clinical trials and they're able to complete large clinical trials very quickly. So we need to do better.
Melanie Cole: Thank you so much, Dr. Winter. What a very interesting episode this was. Thank you again for joining us. And to refer your patient, please visit our website at nm.org/cancer to get connected with one of our providers.
That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. Please remember to subscribe, rate and review this podcast and all the other Northwestern Medicine podcasts. I'm Melanie Cole.