Safety and Efficacy of Infliximab Therapy in the Setting of Steroid-Refractory Acute Graft-versus-Host Disease

Abstract

Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and mortality after allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first-line treatment; however, less than one-half of patients achieve durable remission. Studies suggest that TNF-α, a cytokine released from the bone marrow during conditioning, is involved in the pathogenesis of aGVHD. We retrospectively evaluated the outcome of anti-TNF-α therapy with infliximab in 35 patients with steroid refractory (SR) aGVHD. Infliximab was administered intravenously at 10 mg/kg for a median of 4 doses (range, 1 to 6) on a weekly basis. The overall response rates were 40% (17% complete response [CR], 23% partial response [PR]) at 4 weeks, 23% (9% CR, 14% PR) at 8 weeks, and 17% (all CR) at 12 weeks. Twenty-nine (83%) patients had infectious complications within 12 weeks of initiation of infliximab. These infections included 40 bacterial infections, 6 invasive fungal infections, and 5 viral reactivations. Twelve patients (34%) died secondary to infections. Overall survival at 12 weeks and 6 months from the start of infliximab therapy was 37% (13 of 35) and 17% (6 of 35), respectively; with most deaths secondary to complications from GVHD and infections. In conclusion; the use of infliximab therapy in patients with SR-aGVHD is associated with a modest poorly sustained response along with a heightened risk of severe infections. Future studies with more effective and less toxic therapies are needed for these patients.

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review

“…recorded in 24% of patients. Other studies in patients with SR aGVHD have reported variable rates of infections, including 83% to 100% (34% to 40% fatal) in patients receiving infliximab [15,36,37], 78% to 100% (8% to 50% fatal) in patients receiving alemtuzumab [14,[38][39][40][41][42], and 67% (12% fatal) in patients receiving etanercept [43]. However, many of those series did not categorize infections by severity.…”

“…For patients who develop steroidrefractory (SR) aGVHD, there currently are no proven standard salvage therapies approved by the US Food and Drug Administration or the European Medicines Agency. Several therapies used historically have been assessed as off-label, second-line treatment options, including the chemotherapeutic drug pentostatin [12], antithymocyte globulin (ATG) [13], and monoclonal antibodies including alemtuzumab [14], infliximab [15], and basiliximab/infliximab combination therapy [16]. More recently, ruxolitinib and tocilizumab have been investigated [17][18][19], and a phase I trial of brentuximab vedotin has been conducted [20].…”

Ruxolitinib in children with steroid‐refractory acute graft‐versus‐host disease: A retrospective multicenter study of the pediatric group of SFGM‐TC

“…Several immunosuppressive therapies are used in this indication with variable response rates in childhood. Monoclonal anti‐TNFα (infliximab) have been shown to have response rates between 30% and 60%; however, relapse at discontinuation was very common (approximately 80%) 5,6 . Alentuzumab shows similar response rates (50%‐70%) but mainly effective in cutaneous GVHD 7 .…”

Treatment and unmet needs in steroid-refractory acute graft-versus-host disease

“…In a small study, nine of ten patients responded to treatment; however, four patients died of sepsis [64]. A recent study showed that infliximab therapy in SR-aGVHD was associated with a modest, poorly sustained response along with an increased risk of severe infection [63]; other studies showed similar results [65].…”

“…Infliximab has shown mixed results for the treatment of SR-aGVHD [62,63]. In a retrospective study (N = 68; 51 patients [75%] with grade III/IV), 41 patients (60%) showed response to infliximab therapy at day 7, and 31 patients (46%) showed response at day 28 [62].…”