Combined Cytokine Blocking Therapy (CCBT) Using Basiliximab and Infliximab for Treatment of Steroid-Refractory Graft Versus Host Disease (SR-GvHD)

Background Despite improved advances in graft-vs-host disease (GvHD) prophylaxis regimens and post-allogeneic hematopoietic cell transplant (HCT) supportive care, clinically significant acute GvHD still develops in approximately 30-50% of HCT recipients (Lazaryan A et al. BMT 2016) and often results in increased transplanted-related morbidity and mortality and deterioration of quality of life (Choi J et al. Blood 2012). Standard first-line treatment is high-dose glucocorticoids have been limited including recently approved JAK2 inhibitor (ruxolitinib). The utilization of combined cytokine blockade therapy (CCBT) with the monoclonal antibodies infliximab (a TNF-α inhibitor, INF) and basiliximab (an IL-2 receptor blocker, BAS), has had limited discussion in the literature despite common utilization. The primary objective of this retrospective study was to determine overall response rate (ORR) at days 7, 14 and 28 for CCBT. Secondary outcomes included non-relapse mortality (NRM), and overall survival (OS). Methods 60 patients who met the inclusion criteria were analyzed. Patients included were ≥18 years old and had undergone HCT using any donor or graft source with any conditioning regimen between 2010-2021 at City of Hope Medical Center in Duarte, CA. Patients had steroid refractory aGvHD, according to Mount Sinai Consortium guidelines (Harris AC et al. BMT 2016) and received at least one dose of BAS and at least one dose of INF. Patients with >1 allogeneic transplant, chronic GVHD including overlap syndrome, relapse of primary disease, graft loss, and glucocorticoid treatment for indications other than GVHD were excluded. Treatment BAS was administered intravenously as 20mg doses given first as loading doses on days 1 and 4. Subsequent doses were given weekly starting 7 days after the final loading dose (day 4). INF was administered as 10 mg/kg doses infused weekly. Tacrolimus, sirolimus and cyclosporine dosing and monitoring were performed in accordance with institutional policies. All patients had clinical presentation of SR-GVHD defined as ≥1 of the following: GVHD increasing in stage in any organ or developing in a new organ after 3 days of ≥2 mg/kg methylprednisolone (MSPE) or equivalent, GVHD that has not improved in stage in ≥1 organ after 7 days of ≥2 mg/kg MSPE or equivalent, development of GVHD in a new organ after ≥1 mg/kg MSPE or equivalent for skin GVHD or patients who progress during tapering before a 50% decrease in glucocorticoids is achieve