EBMT 2018 | Understanding the biology of chronic GvHD

Steven Pavletic

Here, Steven Pavletic, MD, MS, from the National Cancer Institute, Bethesda, MD, discusses the previous management of chronic graft-versus-host disease (GvHD), with the BTK inhibitor ibrutinib having been approved for the treatment of patients with chronic GvHD. From the European Society for Blood and Marrow Transplantation (EBMT) 2018 Annual Meeting, held in Lisbon, Portugal, Dr Pavletic also outlines the biology of the disease and how its understanding has been improved significantly with recently conducted research.

Transcript (edited for clarity):

This presentation is part of the section of best clinical trials of the year, where EBMT organized at the end of the annual meeting, very brief summaries of most critical advances in the last year in different areas that are relevant for bone marrow or hematopoietic stem transplantation field.
Here we talk about a first-in-history approved drug for systemic therapy of chronic graft versus host disease.
The significance of this event is illustrated by the fact that this is a result of a communal effort for about a decade, and few years more of the bone marrow transplant community that came together in 2004-2005 to create something that’s called the NIH Consensus Conference for Criteria in clinical trials for chronic graft versus host disease.
At the time, it was recognized that chronic graft versus host disease was a terrible and increasing problem, and new disease created by our treatments, but we don’t have good tools to address it, and moreover, we didn’t have at that time tools to do clinical research and clinical trials properly. So, well-planned trials could result in testing of new agents and hopefully approval of new agents for chronic graph versus host disease.
This 2005 conference followed on from the 2014 conference, that resulted with the evidence-based refined criteria. So at the same time, our knowledge and understanding, because of this communal effort, nationally in the US, internationally working together with EBMT and our colleagues in Europe around the world, our knowledge and understanding of the disease biology of chronic graft versus host disease has dramatically increased as well recently, maybe over the last five years or so.
We have a much better understanding that’s coming together, that chronic graph versus host disease is a chronic disease of a chronically activated immune system that’s misdirected, so sort of an autoimmune disease, we call it allo-immune disease because it’s created by the new allogeneic donor transplanted immune system.
The process results with the damage of target organs, they can be multiple, like eyes, mouth, liver oral mucosa and many others. The signals of damage and information then proliferate through the lymphoid organs, present target antigens to T-cells and B-cells, and create this permanently activated immune dysregulation that at the clinical level we call chronic graft versus host disease.

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