Belimumab Emerges as Potential Prophylaxis for Chronic GVHD Following Allogenic Transplant


Belimumab could be a potential treatment used to prevent chronic graft-vs-host-disease in patients undergoing allogeneic hematopoietic transplantation by inhibiting BAFF and limiting the survival of aforeactive B cells.

Iskra Pusic, MD, MSCI

Iskra Pusic, MD, MSCI

Belimumab could be a potential treatment used to prevent chronic graft-vs-host-disease in patients undergoing allogeneic hematopoietic transplantation by inhibiting BAFF and limiting the survival of aforeactive B cells, according to study results presented at the 2022 Transplantation & Cellular Therapy Meetings.

Belimumab, which is FDA approved for adults with systematic lupus erythematosus and active lupus nephritis, was found to be very well tolerated and also was not linked to any severe infections or myelosuppression when administered to patients in remission from hematologic malignancies.

Overall, 2 out of the 9 patients who received belimumab on study developed moderate to severe cGVHD. One patient died and the other did have an initial response to therapy. 

“These data describe, for the first time, [the] use of belimumab for chronic GVHD prophylaxis,” Iskra Pusic, MD, MSCI, of the Division of Oncology at Washington University School of Medicine in St. Louis, noted in a presentation of the findings. “Belimumab was very well tolerated, and the absence of severe infections and myelosuppression is very reassuring.”

Belimumab is a human monoclonal antibody that functions by preventing B-cell activating factor (BAFF) from binding to its receptors on B cells, thus preventing aforeactive B cells from surviving. Because B cells play an important role in cGVHD pathophysiology and because BAFF plays a substantiated role in cGVHD by promoting BCR signaling, investigators hypothesized that belimumab could be effective at prevention of this disease.

“The coordinated interaction and response between T cells and B cells are required for further perpetuation of chronic GVHD,” Pusic explained. “We know that selective modulation of this alloreactive response rather than general immunosuppression would be a promising mechanism for prevention of GVHD, while still allowing and preserving [the] graft-vs-leukemia effect.”

To that end, this single-center, investigator-initiated phase 1 trial enrolled 9 patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS), and lymphoma to evaluate whether targeting BAFF early after allogenic hematopoietic transplant would have a favorable effect on the incidence or severity of cGVHD.

Enrolled patients were adults in complete remission and tested negative for minimal residual disease 30 days after transplant. Patients had received mobilized peripheral blood stem cells from 10/10 haploidentical-matched related or unrelated donors. Cells received either myeloablative or non-myeloablative conditioning, and tacrolimus, methotrexate, and antithymocyte globulin were allowed. Seven out of the 8 patients were treated with ATG and 1 was treated with posttransplant cyclophosphamide.

Patients received belimumab at 10 mg/kg every 2 weeks for 3 doses followed by 4 more doses at monthly intervals. Treatment initiation began 50 to 80 days following allogeneic hematopoietic cell transplantation.

Patients who received at least 1 dose were evaluable for safety, and patients who received at least 2 doses were evaluable for both safety and efficacy.

The median follow-up time after transplant was 28 months (range, 12-43); the median time since belimumab completion was 23 months (range, 4-29).

Eight of 9 patients successfully received all 7 of the preplanned doses of belimumab. After more than 20 months of follow-up (range, 20-29 months), 5 are alive with no evidence of cGVHD.

Two patients developed cGVHD of the skin, eye, mouth, and liver. For 1 patient, this occurred following their fifth cycle of belimumab; however, their condition improved through treatment with tacrolimus, ruxolitinib (Jakafi), and steroids administered via a tapered schedule. Unfortunately, the other patient died from pneumonia complications after cGVHD occurred 2 months beyond their last belimumab cycle.

Another patient completed all 7 cycles but relapsed with AML 1 month later and was treated with enasidenib (Idhifa) and donor lymphocyte infusion. This patient is now 16 months posttreatment and receiving prednisone for mild oral and upper gastrointestinal cGVHD.

One patient experienced thrombocytopenia and consequently had to reduce their dose to 3 cycles—3 months later, this patient relapsed with lymphoma. Three patients developed stage 1 skin acute GVHD; 2 cases resolved completely with a steroid pulse, and 1 case developed into overlap cGVHD.

No adverse events equal to or greater than grade 3 were reported. There were also no signification infections or myelosuppression, although 1 patient had cytomegalovirus reaction. No patients demonstrated any infusion reactions or hypersensitivity.

“While the result of our study really needs further validation in a larger trial to further assess the impact of belimumab on incidences of chronic GVHD, these preliminary results are encouraging,” Pusic said.

Furthermore, risk stratification should be an important consideration in future studies, she concluded, noting that correlative studies have been launched because B-cell reconstitution was delayed.


  1. Pusic I, Johanns T, Sarantopoulos S, et al. Use of belimumab for prophylaxis of chronic graft-versus-host disease. Presented at: 2022 Tandem Meetings Transplantation & Cellular Therapy Meetings of ACTCT and CIBMTR; April 23-26, 2022; Salt Lake City, UT. Abstract 34.
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