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PTCL Community Treatment and Future Advancements

Insights From: Neha Mehta-Shah, MD, Washington University School of Medicine in St. Louis
Published: Monday, Jan 28, 2019



Transcript: 

Neha Mehta-Shah, MD: Dr Chadi Nabhan at ASH [the American Society of Hematology Annual Meeting & Exposition] this year presented a retrospective review of about 200 patients who have peripheral T-cell lymphoma across a number of subtypes. The purpose of this was to look at a real-world experience with peripheral T-cell lymphomas in the United States. He had shown that the median survival for these patients again is about 6 months, although there’s a subset of patients who certainly have much longer remissions. And when you look at his curves, it looks as if there’s a percentage of people who may have been cured with their second or third line of therapy. It was clear from the work that he presented that up-front autologous transplant for consolidation was not as commonly practiced in the community as it may be at certain large academic centers. But it’s hard to draw conclusions, as the patient populations may be notably different.

I think there are still a lot of questions left to answer in peripheral T-cell lymphomas. I think specifically in the relapsed/refractory setting, there are a number of either combinations of therapies that are currently being used or novel therapies that are being explored. So, for example, we had published previously on the combination of romidepsin and lenalidomide and romidepsin, lenalidomide, and carfilzomib in 2 independent studies in peripheral T-cell lymphoma, which look like they have overall response rates in the 40% to 50% range. The response rates are higher, near 100% in angioimmunoblastic T-cell lymphoma [AITL] from these combinations, and so there’s a clear push in the T-cell lymphoma community of experts to start to identify which histologies benefit from certain types of drugs. And maybe angioimmunoblastic T-cell lymphoma should be treated differently from other types of peripheral T-cell lymphoma, especially in the relapsed setting.

Similarly, Owen O’Connor’s group at this meeting is presenting on romidepsin and 5-azacitidine, which also looks very promising in angioimmunoblastic T-cell lymphoma. And there are efforts through the US Intergroup to consider comparing these therapeutic strategies head-to-head, but that is being explored. Additionally, there is a role for PI3 [phosphatidylinositol 3]–kinase inhibition in peripheral T-cell lymphomas as well. Dr Steven Horwitz and colleagues presented on duvelisib in combination with romidepsin or duvelisib in combination with bortezomib at this meeting, as well, with response rates of 50% to 60% and some of those responses being quite durable. In fact, some were so deep that they led patients to move on to an allogeneic transplant, and so that’s also a promising strategy. Duvelisib is being explored in a national phase II study in peripheral T-cell lymphomas to better identify the efficacy in these rare diseases.

So I think there are a number of potential new strategies that are being explored by ourselves and many of my colleagues to try to improve the care for people with peripheral T-cell lymphomas overall and to try to develop therapies that are tolerable and also long term for those who cannot get an allogeneic stem cell transplant. And we’re also investigating the role of transplant itself further in peripheral T-cell lymphomas and identifying who best benefits from this.

I think the other challenge that we face is that the histology is not as well understood, and the pathophysiology is not always as well understood in peripheral T-cell lymphomas. And so we’re learning that a group of people who have PTCL NOS [not otherwise specified] may in fact really have, by gene expression profiling or by genomic sequencing, …AITL or a different disease. And because we have better understanding of the biology of these diseases, we’ll be better equipped to develop new therapies for them.

As a junior investigator who is devoted to improving the care of peripheral T-cell lymphoma, I think it’s a very exciting time. I think the results of ECHELON-2 are the first in peripheral T-cell lymphoma to show a survival benefit, which is incredibly exciting for our community. And then we’re very hopeful, as we develop new therapies and have better understanding of the biology of these diseases, that we’ll be able to move the bar forward both for patients in the up-front setting and, hopefully, also in the relapsed/refractory setting.

Transcript Edited for Clarity
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Transcript: 

Neha Mehta-Shah, MD: Dr Chadi Nabhan at ASH [the American Society of Hematology Annual Meeting & Exposition] this year presented a retrospective review of about 200 patients who have peripheral T-cell lymphoma across a number of subtypes. The purpose of this was to look at a real-world experience with peripheral T-cell lymphomas in the United States. He had shown that the median survival for these patients again is about 6 months, although there’s a subset of patients who certainly have much longer remissions. And when you look at his curves, it looks as if there’s a percentage of people who may have been cured with their second or third line of therapy. It was clear from the work that he presented that up-front autologous transplant for consolidation was not as commonly practiced in the community as it may be at certain large academic centers. But it’s hard to draw conclusions, as the patient populations may be notably different.

I think there are still a lot of questions left to answer in peripheral T-cell lymphomas. I think specifically in the relapsed/refractory setting, there are a number of either combinations of therapies that are currently being used or novel therapies that are being explored. So, for example, we had published previously on the combination of romidepsin and lenalidomide and romidepsin, lenalidomide, and carfilzomib in 2 independent studies in peripheral T-cell lymphoma, which look like they have overall response rates in the 40% to 50% range. The response rates are higher, near 100% in angioimmunoblastic T-cell lymphoma [AITL] from these combinations, and so there’s a clear push in the T-cell lymphoma community of experts to start to identify which histologies benefit from certain types of drugs. And maybe angioimmunoblastic T-cell lymphoma should be treated differently from other types of peripheral T-cell lymphoma, especially in the relapsed setting.

Similarly, Owen O’Connor’s group at this meeting is presenting on romidepsin and 5-azacitidine, which also looks very promising in angioimmunoblastic T-cell lymphoma. And there are efforts through the US Intergroup to consider comparing these therapeutic strategies head-to-head, but that is being explored. Additionally, there is a role for PI3 [phosphatidylinositol 3]–kinase inhibition in peripheral T-cell lymphomas as well. Dr Steven Horwitz and colleagues presented on duvelisib in combination with romidepsin or duvelisib in combination with bortezomib at this meeting, as well, with response rates of 50% to 60% and some of those responses being quite durable. In fact, some were so deep that they led patients to move on to an allogeneic transplant, and so that’s also a promising strategy. Duvelisib is being explored in a national phase II study in peripheral T-cell lymphomas to better identify the efficacy in these rare diseases.

So I think there are a number of potential new strategies that are being explored by ourselves and many of my colleagues to try to improve the care for people with peripheral T-cell lymphomas overall and to try to develop therapies that are tolerable and also long term for those who cannot get an allogeneic stem cell transplant. And we’re also investigating the role of transplant itself further in peripheral T-cell lymphomas and identifying who best benefits from this.

I think the other challenge that we face is that the histology is not as well understood, and the pathophysiology is not always as well understood in peripheral T-cell lymphomas. And so we’re learning that a group of people who have PTCL NOS [not otherwise specified] may in fact really have, by gene expression profiling or by genomic sequencing, …AITL or a different disease. And because we have better understanding of the biology of these diseases, we’ll be better equipped to develop new therapies for them.

As a junior investigator who is devoted to improving the care of peripheral T-cell lymphoma, I think it’s a very exciting time. I think the results of ECHELON-2 are the first in peripheral T-cell lymphoma to show a survival benefit, which is incredibly exciting for our community. And then we’re very hopeful, as we develop new therapies and have better understanding of the biology of these diseases, that we’ll be able to move the bar forward both for patients in the up-front setting and, hopefully, also in the relapsed/refractory setting.

Transcript Edited for Clarity
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TitleExpiration DateCME Credits
Oncology Consultations®: The Advancing Role of CAR T-Cell Therapies in Hematologic MalignanciesApr 30, 20191.5
Advances in™ Diagnostic Guidelines for Effective Clinical Decision - Making in the Management of Hematologic MalignanciesApr 30, 20191.5
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