The 2022 Tandem Meetings | Use of belimumab for prophylaxis of chronic GvHD

So this was a pilot study that we ran and are still running actually at WashU, where the idea was to use belimumab for the prophylaxis of chronic GvHD. Belimumab is a monoclonal antibody against BAFF and binding BAFF to BCR receptor B cells. The idea was is that by depleting these autoreactive B cells, we could prevent the development of chronic GvHD.

Belimumab is an FDA approved drug for the treatment of lupus and lupus nephritis, so there is dosing and safety data that we are already aware of. We elected to use the same schedule of dosing, which is 10 mg/kg. It’s given initially every two weeks for three doses, and then we are giving it for four more doses at monthly intervals so it ends up being total of seven doses for about six months. We would start it anywhere between day 50 and day 80 post-transplant. So we would establish that these patients are in complete remission after transplant. Patients were all adults with hematological malignancies, and mostly these were AML and ALL and then few patients with MDS and few patients with lymphoma. We were planning a total of 10 patients, and I presented data on first nine patients. The last patient is already enrolled and has been through the first two or three doses by now. As I said, so they all had to be in complete remission. They all received peripheral blood stem cell transplant from 10 out of 10 matched donors who could be either related or unrelated. Then GvHD prophylaxis was with methotrexate and tacrolimus, and then we allowed patients to receive ATG. I think seven to nine of them have received ATG. The primary endpoint really was to see how they’re going to tolerate belimumab, so safety, and then also to get some information on preliminary efficacy and what’s going to happen with their acute and particularly chronic GvHD. So far, I mean, among all these patients, really nobody had three or more adverse events. There were no any infusion reactions or hypersensitivity, and also importantly, there were no major infections. There was one patient who had CMV reactivation, but there was no significant infection or myelosuppression. The counts stayed preserved. In regards to acute GvHD, three patients had very mild grade 1 skin GvHD, and one went on to develop overlap chronic, and two completely resolved with a brief pulse of steroids. Then, in regards to chronic GvHD, so out of these nine patients, eight completed all doses as planned, and we have been following them now more than 20 months down the road. Out of these eight, five had no chronic GvHD and are not on any immunosuppression now, 20 months past them finishing belimumab. Then two patients had some chronic GvHD, one had very mild to moderate, responded to a little bit of immunosuppression and then GvHD kind of faded away. He’s now on a tapering schedule, I think just on 5 mg of prednisone. The other one had more severe chronic GvHD. He also had a lot of complications from hemochromatosis and fatty liver, and he developed that chronic GvHD about seven months after he finished belimumab. He eventually then passed away from pneumonia and liver failure. But really those two patients were the only two who had more significant chronic GvHD.

So overall, I think this is promising data. Our correlative studies are really in process because we are waiting for this last patient to be enrolled. But so far just immune reconstitution is showing that the B-cells are depressed a year throughout after transplant. But it will be interesting to see the measures of BAFF and correlate them with B-cell levels. I think it’s going to be interesting, and hopefully we can make it into a bigger study and really see on a larger group of patients how this will play out. But I think the safety here was really, I think, most important to come across that the drug was well tolerated and that there was no myelosuppression or infections.