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Additional Advances in Graft-Versus-Host Disease Research and Clinical Trials With Shernan Holtan, MD

At the 2022 American Society of Hematology (ASH) Annual Meeting, Dr. Shernan Holtan, Associate Professor at the University of Minnesota Medical School, presented a late-breaking abstract on the BMT CTN 1703 trial of post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil as graft-versus-host disease (GVHD) prophylaxis after allogenic hematopoietic cell transplantation. Prior to the presentation, she sat down with Oncology Data Advisor to preview the trial's promising results and its potential to transform practice for GVHD.  

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. I'm Keira Smith. Today, I'm here at the ASH Annual Meeting with Dr. Shernan Holtan, who is here to talk about the results of the BMT CTN 1703 trial that she is presenting.

Shernan Holtan, MD: Thanks for having me. We're really lucky to be able to present the 1703 data. This is a phase 3 clinical trial that literally just had the data cutoff a few months ago. This is a randomized phase 3 study testing a novel GVHD prophylaxis regimen.

Since the mid-1980s, we've used a calcineurin inhibitor and methotrexate as the standard doublet for GVHD prophylaxis in the United States. This trial was testing a regimen of post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil (MMF) against the standard. Indeed, as you can see from the abstract, the experimental arm with post-transplant cyclophosphamide did have improved outcomes. The primary end point of the study was graft-versus-host disease–free/relapse–free survival.

We thought this was important. A number of previous studies have shown that we can greatly reduce the risk of acute and chronic graft-versus-host disease, but often this comes at an expense, either increased risk of infections that could be fatal or increased risk of relapse. We wanted to test whether we could improve upon the outcomes of patients with GVHD while not making these other issues worse. That's why we chose that primary end point, and indeed, the experimental arm is the winner.

Oncology Data Advisor: That's great. What were the specific results of the trial?

Dr. Holtan: Specifically, that one-year graft-versus-host disease–free/relapse-free survival was about 16% to 17% higher in the experimental arm. We powered the study to be able to detect a minimum difference of that type of magnitude. We thought that this would be clinically meaningful. We didn't want to do a study that would just require, say, a 5% improvement or even a 10% improvement even to constitute a really clinically meaningful change. We thought we had to have at least a 15% difference between the arms, and indeed, we saw more than that.

Since we saw that magnitude of benefit, our expectation and our hope is that this will actually change the standard of care. This should change practice because it really was a meaningful difference.

Oncology Data Advisor: Great, that's so exciting.

Dr. Holtan: Yes, thank you.

Oncology Data Advisor: Anything else you'd like to share about your research or about your experience at ASH as a whole?

Shernan Holtan: Yes, absolutely. This is a great opportunity to share other research as well, and some complementary research too. Our big focus here is on the 1703 abstract, but there's a limitation to the study in that it's only adults and it's only in the reduced-intensity transplant setting. This does not address pediatric transplantation, and it does not address myeloablative conditioning.

We had another abstract that was a single-center study from the University of Minnesota. It tested the same GVHD prophylaxis platform as 1703, but in the myeloablative setting, including pediatrics and adults. It just so happens that we were able to present that abstract at this meeting as well. Dr. Alex Hoover, one of our fellows, presented our phase 2 findings that showed, just like the 1703 trial, very low rates of acute and chronic graft-versus-host disease with post-transplant cyclophosphamide. There was no increase in relapse progression, and in fact, there an improvement in overall survival compared with our historical cyclosporine and methotrexate.

This really complements what we found in 1703, that both in the myeloablative setting and the reduced-intensity setting, post-transplant cyclophosphamide is associated with very low rates of severe acute and chronic graft-versus-host disease.

Oncology Data Advisor: Great, thanks so much for sharing all this. It's so exciting to hear about.

Dr. Holtan: Yes, thank you. Stay tuned for the publications. They'll be forthcoming. They'll have a lot more data and a lot more subgroup analysis, because I'm certain that everyone has a question—well, what about this particular disease? Or what about this particular age group? Just stay tuned; more will be revealed. I'm just excited to be able to share these top-line results with everyone.

Oncology Data Advisor: Great, looking forward to hearing that. And best of luck on your presentation.

Dr. Holtan: Thank you so much.

Thank you for listening to this podcast recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at https://conveymed.io/ and OncData.com. Don't forget to follow us on social media for news, exclusive interviews, and more.

About Dr. Holtan

Shernan Holtan, MD, is an Associate Professor of Medicine in the Division of Hematology, Oncology, and Transplantation at the University of Minnesota Medical School. She specializes in allogeneic hematopoietic cell transplantation for malignant and non-malignant diseases, as well as long-term survivorship needs. Her research focuses on personalized immune monitoring, inflammation resolution, wound healing–associated growth factors in graft-versus-host disease, and the role of strength training on late effects related to transplantation.

For More Information

Holtan SG, Hamadani M, Wu J, et al (2022). Post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil as the new standard for graft-versus-host disease (GVHD) prophylaxis in reduced intensity conditioning: results from the phase III BMT CTN 1703. 64th American Society of Hematology Annual Meeting. Abstract LBA-4.

Hoover A, O'Leary D, Cao Q, et al (2022). Phase II study of myeloablative 8/8- or 7/8-matched allotransplantation with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil: marked reduction in GVHD risk without increased relapse risk compared to historical cyclosporine/methotrexate. 64th American Society of Hematology Annual Meeting. Abstract 114.

Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor. 

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