Begelomab Salvages Steroid Resistant Acute Graft Versus (SR aGVHD) Host Disease in Pediatric Patients: A Single Center Case Serie

Graft-versus-host disease (GvHD) remains a major cause of mortality and morbidity, especially when steroid-refractory (SR). Begelomab is a murine monoclonal antibody that targets dipeptidyl peptidase 4 (CD26) on T cells. Begelomab exerts its immunomodulatory effect by inhibiting CD26-associated signaling and the secretion of pro-inflammatory cytokines.A previous study in adult patients with aGVHD showed promising results: 75% response rate by day 28 and >50% overall response in grade III/IV acute (a) GvHD. Here, we present our experience with pediatric patients who received Begelomab for SR aGvHD.Five patients (3-20 years) received Begelomab for SR aGVHD at Stanford Children's Health from 2017 to 2021 (IRB#4134, 46969). Lymphocyte subsets of one of these subjects were analyzed before and after treatment with Begelomab using a Lyric 10-color flow cytometry instrument.Four patients had acute leukemia, while 1 had focal segmental glomerulosclerosis and received HSCT from his designated kidney donor for immune tolerance induction (Table 1). The diagnosis of aGvHD occurred between day 10 to 32 post-HSCT, and all patients had grade IV aGVHD before receiving Begelomab. The time from aGVHD diagnosis to initiating Begelomab ranged from 28 to 112 days, with a median of 63 days.Begelomab was administered intravenously at a dosage of 2.7mg/m2/day on days 1, 2, 3, 4, 5, 10, 14, 17, 21, 24, and 28, totaling 11 doses (). At the time of Begelomab administration, all patients were receiving systemic steroids and at least 2 other second-line agents, such as calcineurin inhibitors, infliximab, basiliximab, ruxolitinib, ECP, and alpha-1 antitrypsin.No adverse events were reported. Two patients expired before the response to Begelomab could be assessed. Of the remaining patients, 2 achieved complete response by Day 21 and successfully tapered off systemic steroids. The reamining patient, with controlled aGvHD, discontinued all immunosuppressive medications except tacrolimus within 6 months.Assessment of CD26 expression before and after Begelomab infusion in one patient showed high expression of CD26 in circulating CD3+CD4+ T cells (>20%). As expected, Begelomab did not downregulate the CD26 target or eliminate CD26+ T cells. Instead, it bound to CD26+ T-cells, inducing internalization of the CD26 complex and inhibiting CD26-associated signaling.In conclusion, our study in heavily pretreated pediatric patients with grade III-IV SR aGvHD demonstrates the promising safety and efficacy of Begelomab. No adverse events were reported, highlighting its excellent tolerability. A significant proportion of patients achieved complete response and were able to taper off systemic steroids. However, further large-scale clinical trials involving both adults and pediatric patients are needed to thoroughly evaluate the efficacy of Begelomab in the treatment of SR aGvHD.