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ASH 2021 | Prophylactic belimumab against chronic GvHD

John DiPersio, MD, PhD, Washington University School of Medicine, Saint Louis, MO, describes the role of belimumab, a monoclonal antibody currently approved in systemic lupus erythematosus (SLE) that targets B-cell activating factor (BAFF), in preventing chronic graft-versus-host disease (cGvHD). As BAFF plays a role in B-cell activation, which is thought to mediate cGvHD, belimumab is hypothesized to act as a prophylaxis against cGvHD. In a pilot study, prophylactic belimumab was well tolerated and reduced rated of cGvHD. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

Belimumab is an antibody. So, GvHD is either acute or chronic, acute GvHD is mediated by T-cells, alloreactive effector T-cells and it’s the T-cells in the product that mediate this. Chronic GvHD is a different process that actually depends upon both T-cells. The T-cells are often generated from the stem cell product instead of the infused T-cells, but T-cells are essential and B-cells.

And so B-cells actually are the cells that get activated by this chronic T-cell activation and that chronic B-cell activation results in the production of antibodies, which have broad spectrum of re- activities...

Belimumab is an antibody. So, GvHD is either acute or chronic, acute GvHD is mediated by T-cells, alloreactive effector T-cells and it’s the T-cells in the product that mediate this. Chronic GvHD is a different process that actually depends upon both T-cells. The T-cells are often generated from the stem cell product instead of the infused T-cells, but T-cells are essential and B-cells.

And so B-cells actually are the cells that get activated by this chronic T-cell activation and that chronic B-cell activation results in the production of antibodies, which have broad spectrum of re- activities. And much like an autoimmune patient with lupus or mixed connective tissue disease these antibodies combine to tissues and cause all sorts of things like plural effusions, pericardial effusions, thickening of the skin, deep pigmentation of the skin, dry eyes, dry mouth that can be mild, moderate or life-threatening.

And chronic GvHD is a disease which can be just horrible in patients. And so again, we thought that there’s two ways to block chronic GvHD, just like acute GvHD needs to be pursued early in the transplant setting. And so if you block acute GvHD, you’re going to block chronic GvHD, but if you are not completely effective early on there are going to be B-cells that get activated later on that make antibodies.

And so we thought that if we could prophylactically block the interaction of T-cells with B-cells in an early fashion, that we could prevent that B-cell activation and prevent the process of chronic GvHD.

And that’s what we did in this pilot study. We gave a drug called Belimumab, which is a BAFF inhibitor. BAFF is B-cell activating factor. It’s made by activated T-cells and that’s the thing that we think is one of the proteins that activates B-cells to produce these antibodies. So we gave it prophylactically to prevent the B-cells from being activated. And we showed very low rates of chronic GvHD. But the caveat is that this is a small pilot study and it would have to be done in a perspective randomized fashion. And hopefully we can do that in the future.

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