Introduction: Belimumab (BEL) is a monoclonal antibody which inhibits binding of B-cell-activating factor (BAFF) to its receptors on B cells, thus inhibiting the survival of alloreactive B cells. Given the role of B cells and BAFF in chronic Graft-versus-Host Disease (cGvHD) pathophysiology, BEL might have a role in prevention of cGvHD. We hypothesized that targeting BAFF early after allogeneic hematopoietic cell transplantation (alloHCT) would be well-tolerated and have a favorable effect on the incidence and severity of cGvHD.
Methods: We are presenting data on the first 9 Pts. All Pts were adults in complete remission after alloHSCT, using mobilized peripheral blood grafts from matched related or unrelated donors, after any conditioning. cGvHD prophylaxis was with tacrolimus and methotrexate. BEL was administered i.v. at 10 mg/kg Q2W for 3 doses followed by 4 monthly doses, for a total of 7 doses, starting 50-80 days after alloHCT. Pts who received ≥1 dose of BEL were evaluable for safety and ≥2 doses for efficacy assessment. cGvHD was diagnosed using the NIH criteria. All analyses are descriptive.
Results: BEL was well tolerated. There were no reported grade >3 treatment-related AEs, no significant infections or myelosuppression, and no infusion reactions. 8/9 Pts received all 7 doses of BEL. Of those 8 Pts, 5/8 Pts have no evidence of cGvHD and are completely off immunosuppression > 20 mo after completing BEL. 2/8 Pts developed cGvHD: 1 Pt developed moderate cGvHD of skin, eye, mouth and liver around cycle 5 of BEL and improved with therapy; 1 Pt developed cGvHD of skin, eye, liver 7 mo after completing BEL and died of complications of pneumonia and liver failure (also Hx of hemochromatosis). 1/8 relapsed with AML 1 mo after completing BEL; now in remission after further treatment. 1/9 Pts stopped BEL after only 3 doses, due to thrombocytopenia and insurance issues. He was found to have relapsed lymphoma 3 mo later, achieved remission with further treatment and has no evidence of cGvHD 20 mo after stopping BEL. One additional Pt is being enrolled. Immune reconstitution studies are showing that B-cell counts remain low 1 yr out of alloHCT in all Pts.
Impact: This data describes for the first time the use of BEL for cGvHD prophylaxis. Absence of severe infections and myelosupression is reassuring. While more Pts are needed to further assess the impact of prophylactic BEL on the incidence of cGvHD, these preliminary results are encouraging.
Organization – Washington University in St. Louis
Pusic I, Johanns T, Sarantopoulos S, Westervelt P, Cashen A, Uy G, Abboud C, DiPersio J