Editor’s Note: The 2025 China-Europe Scientific Forum on Blood and Marrow Transplantation and Cellular Therapy was recently held successfully in Guangzhou. The conference was co-hosted by the Hematology Branch of the China International Exchange and Promotive Association for Medical and Health Care (CPAM) and the Shanghai Representative Office of the European Society for Blood and Marrow Transplantation Foundation (EBMT, Netherlands). It was jointly organized by the National Clinical Research Center for Hematologic Diseases – Institute of Hematology, Peking University, Sun Yat-sen University Cancer Center, and the Second Xiangya Hospital of Central South University.
At the forum, Professor Olaf Penack from Charité – Universitätsmedizin Berlin delivered an insightful presentation titled “GVHD – standard management in Europe and upcoming strategies” offering a comprehensive overview of the latest advances and future directions in graft-versus-host disease (GVHD) management across Europe.Oncology Frontier-Hematology Frontier conducted an in-depth interview with Prof. Penack at the conference to further explore these important topics.
Oncology Frontier-Hematology Frontier：Graft-versus-host disease (GVHD) remains one of the most common and serious complications following hematopoietic stem cell transplantation, significantly affecting patient survival and quality of life. Europe has developed relatively systematic strategies for the standard prevention and treatment of GVHD. Could you elaborate on the key components of these standard management approaches, and what notable outcomes have been achieved in clinical practice?
Professor Olaf Penack：Absolutely. I’m happy to comment on the key components of GVHD management in Europe. Europe. So we are publishing the recommendations of the EBMT, and I think most important is really prophylaxis of graft-versus-host disease. So we now recommend to use either antithymocyte globulin (ATG) or post-transplant cyclophosphamide in matched-related, matched-unrelated, and mismatched-unrelated setting. In the haplo setting we’re recommending post-transplant cyclophosphamide, which is, I think, also standard of care worldwide.
When coming to the treatment, first-line treatment of acute and chronic GVHD remains to be steroids. And relatively new in the last years, ruxolitinib has become the standard therapy of steroid-refractory acute and as well as chronic GVHD. When we’re now talking about third-line treatment in the setting of acute GVHD, there is no approved standard so far and currently trials are running. We have different manufacturers interested here and I hope that we can make progress in the near future.
In the setting of chronic GVHD, outside of Europe, we have already approved drugs such as belumosudil in some parts of the world, I believe in the US, in the UK, in Japan, for instance. And ibrutinib is also approved, at least in the US.In Europe, we don’t have approved options. We are using options which are, as mentioned, approved in the other countries.But we’re of course also focusing on clinical trials in this setting.
Oncology Frontier-Hematology Frontier：With advances in immunology and precision diagnostics, early identification and risk stratification have become essential for improving GVHD outcomes. What are the latest developments in Europe regarding early diagnosis and the use of biomarkers for GVHD? How have these innovations positively impacted patient prognosis?
Professor Olaf Penack：Yeah, I mean, I must say that is that part of GVHD is not really a success story so far, at least in Europe. Of course, there have been many publications on biomarkers, which can be used. Some of them are also validated, when you think of the biomarkers by the MAGIC consortium from the US. Also, other biomarkers have been tested. But to be very honest, they are not broadly used in clinical standard. For instance, the MAGIC biomarkers — it’s very difficult to get them in Europe. We’re currently trying to bring them to Europe so that investigators and physicians can offer these biomarkers. So I think that is still a pretty long way to go.
Everybody appreciates, I think, that an early detection of graft-versus-host disease and early treatment is much, much better, and we’re working on it. But to very precisely answer to the question — so which differences did it already make for current management and patients? I think that part is really disappointing. And I have to say currently there was the translation of the progress which is there in clinical trials to standard practice has not happened.
Oncology Frontier-Hematology Frontier：Refractory and relapsed GVHD continue to pose significant clinical challenges. What novel therapeutic approaches or ongoing clinical trials are currently being pursued in Europe for these difficult cases? In your opinion, which of these emerging therapies holds the greatest promise for reshaping the future treatment landscape of GVHD?
Professor Olaf Penack：Yes, so I think for patients with refractory GVHD, it is well known that these patients have a worse outcome and clinical trials are needed. So most of these patients have been treated with multiple immunosuppressive drugs. So I think the options which do not only target T-cell biology are most promising. I would like to mention two approaches here.
One, there is axatilimab, an antibody targeting the CSF1 receptor, which is mostly expressed on myeloid cells such as macrophages. It is a novel treatment in chronic GVHD. And it not only inhibits inflammation, but it also directly targets fibrosis. So I think that is very promising.
And I would also like to highlight the treatment with microbiota. There are currently trials ongoing with allogeneic microbiota products in refractory acute GVHD and as prophylaxis of graft-versus-host disease around allotransplant. And I think that is also a very new development and it holds promise.
Oncology Frontier-Hematology Frontier：The management of GVHD is increasingly moving toward personalized and multidisciplinary care models. How do you view the current progress and challenges in implementing individualized treatment strategies and cross-disciplinary collaboration in Europe? In what ways could these approaches enhance outcomes for GVHD patients in the future?
Professor Olaf Penack：I think the critical point is really multidisciplinary teams. I think they are absolutely important for patient care. And on the same side, they are not so easy to achieve. Because hematologists need to reach out to other disciplines and need to involve them. So in most centers, hematologists have contacts to some disciplines, but it’s very difficult to really build and hold up a really multidisciplinary team which stays. So I can also confirm from my center — there are doctors from disciplines which seem to be more interested in stem cell transplantations and others are not. And it’s not so easy, because how do we want to give them — how is it possible to give them incentives for doing that? So it is a challenge, but I think a critical point. And I think we should really focus on building up these teams and really appreciating that they’re critical for our patients.
