P1295: ADVANTAGE OF FIRST-LINE TDM-DRIVEN USE OF INFLIXIMAB FOR TREATING ACUTE INTESTINAL AND LIVER GVHD IN CHILDREN: A PROSPECTIVE, SINGLE-CENTER STUDY.

Topic: 22. Stem cell transplantation - Clinical Background: Currently, there is no commonly accepted treatment for patients with steroid-refractory (SR) acute graft-versus-host disease (aGVHD). Inhibition of TNF-α has been suggested in all phases of aGVHD treatment, as prevention, as part of primary treatment, and most commonly as a treatment for steroid-refractory or steroid-dependent aGVHD. Aims: The aim of this study was to assess the effectiveness of first-line infliximab treatment compared with infliximab use in second or further-line therapy in pediatric alloHSCT recipients. Further, the study aims to investigate whether the drop in infliximab plasma concentrations could be associated with clinical response and production of proinflammatory and anti-inflammatory cytokines. Methods: This prospective, single-center, observational study was carried out at the pediatric Bone Marrow Transplant Center of the Institute for Maternal and Child Health – IRCCS Burlo Garofolo, Trieste, Italy, from 2018 to 2022. All patients underwent alloHSCT after myeloablative conditioning. All patients received infliximab biosimilars Inflectra® or Flixabi® at the standard dose of 10 mg/kg/dose intravenously in two hours infusions, on a weekly basis. Infliximab treatment in a second or further-line therapy for SR or steroid-dependent aGVHD was defined as standard infliximab use. Infliximab treatment started together or in the first three days of steroid treatment as part of the first-line treatment, defined as early infliximab use. All patients underwent proactive infliximab TDM with anti-drug antibodies detection. In addition, 27 pro-inflammatory and anti-inflammatory cytokines’ blood levels were also measured at baseline and subsequently for every infliximab TDM. Results: Of 28 patients, fourteen received infliximab for steroid-refractory or steroid-dependent aGVHD (Standard Group), and the remaining used infliximab as part of the first-line therapy (Early Group). Two months after the initiation of treatment, in the Standard Group, organ-specific responses were 14% (n = 1 complete response (CR), n = 1 partial response (PR)), 36% (n = 2 CR, n = 3 PR), and 86% (n = 2 CR, n = 10 PR) for skin, gastrointestinal, and liver involvement, respectively. While in the Early Group, 14 patients (100%) with gastrointestinal and liver aGVHD obtained CR and 2 patients (7%) with skin involvement obtained PR (Figure 1). Skin involvement demonstrated poor response to both early and standard administration. No adverse reactions were observed during infliximab infusions. No bacterial or fungal infections or deaths due to infections have been recorded during the follow-up period. Statistically significant differences between the two groups were found for IL-7, IL-13, MIP-1β, IP-10, MIP-1a, and IL-4 serum levels. Summary/Conclusion: To the best of our knowledge, our study is the only one focusing on using infliximab as the first-line TDM-driven therapy for treating aGVHD in children. Our data suggest that the response to infliximab is organ related. The earlier the administration of infliximab, the better the clinical outcome achieved in children with intestinal and liver aGVHD. Future multi-center randomized controlled trials may verify our preliminary observation in using infliximab as part of the primary treatment for intestinal and liver aGVHD.Figure 1. Organ-specific responses after two months of treatment Keywords: Pediatric, Infliximab, Graft-versus-host disease (GVHD)