Acute Graft versus Host Disease (AGvHD) is quite common following unrelated donor stem cell transplants. Severe instances of AGvHD (grade 3-4) are a major cause of death, especially after HLA-mismatched donors. [HLA stands for Human Leukocyte Antigens, proteins on the surface of cells that regulate the immune system]. It stands to reason then, that a mismatch of these proteins between the stem cell donor and the stem cell recipient are bound to create some difficulties for the recipient. Matching is usually graded on a scale of 1-8, though sometimes also on scales of 1-10 or 1-12. The higher the matching number, the better the match between donor and recipient.
There are no approved agents to prevent AGvHD and that provides ample reason to look for novel therapeutics.
The most recent issue of the Journal of Clinical Oncology provides a very interesting article that summarizes the effect of adding the injectable arthritis drug Orencia (abatacept), indicated for the treatment of rheumatoid arthritis to a combination of two drugs currently used to, hopefully, prevent the onset of AGvHD (one of those drugs is methotrexate, [MTX] the other is a calcineurin inhibitor [CNI] such as, e.g., tacrolimus).
Researchers completed two Phase II studies in adults and children with hematologic malignancies:
The results are exciting and can be summarized as follows :
The authors conclude:
“Adding abatacept to [unrelated donor stem cell transplants] was safe, reduced AGVHD, and improved severe AGvHD survival at +180 days. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched stem cell transplants.” [Emphasis added]
It will most likely take 1-2 years before we will see this mix of products in clinical practice for allo-stem cell transplants, as the manufacturer of Orencia (Bristol Myers Squibb) will need to secure FDA approval for future use. Either way, this outcome is a major step forward in the treatment of patients who receive transplant from an unmatched, unrelated donor.
about the author
I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.