High-dose corticosteroids with or without etanercept for the treatment of idiopathic pneumonia syndrome after allo-SCT

Abstract

Idiopathic Pneumonia Syndrome (IPS) is a common complication after allo-SCT and results in high mortality rates. Conventional treatment for IPS typically includes supportive care and high-dose corticosteroids (CS). Data suggests that TNF-a is important in the pathogenesis of IPS and that the TNF-a inhibitor etanercept may be useful for IPS treatment. We performed a retrospective comparison of consecutive patients treated at our center for IPS with CS only from 1999 to 2003 (group 1, n ¼ 22) or CS plus etanercept from 2004 to 2007 (group 2, n ¼ 17). In all, 18% of patients in group 1 vs 53% in group 2 were successfully taken off respiratory support and discharged from the hospital (P ¼ 0.039). OS was significantly better for recipients of CS plus etanercept (P ¼ 0.003). The estimated survival at 28 days and 2 years after IPS was 36.4% (95% CI 17 --56%) and 9.1% (95% CI 2 --25%) for group 1 and 88.2% (95% CI 61 --97%) and 18% (95% CI 4 --38%) for group 2, respectively. Our retrospective comparison suggests that the addition of etanercept to CS for IPS improves response rates and OS. However, outcomes remain limited in both groups, highlighting the need for more effective interventions to treat early and late complications of IPS.

Randomized, Double-Blind, Placebo-Controlled Trial of Soluble Tumor Necrosis Factor Receptor: Enbrel (Etanercept) for the Treatment of Idiopathic Pneumonia Syndrome after Allogeneic Stem Cell Transplantation: Blood and Marrow Transplant Clinical Trials Network Protocol

“…Historically, early response and overall survival have been poor (<50%) when IPS was treated with systemic corticosteroids plus supportive care measures alone. In the past decade, significant improvements in day 28 survival (>70%) were reported in 2 limited institution studies combining etanercept with systemic corticosteroids [7,8]. In the current study, the day 28 response (67%) and survival (72%) noted in the corticosteroid (plus placebo) arm greatly exceeded historical reports using corticosteroids as primary management (Table 6), whereas 1-year survival remained poor (16.7%).…”

“…More recently, the use of TNF inhibitors was proposed, with potential benefits noted in single or limited institution studies [7,8,14]. In particular, clinical trials combining a soluble TNF binding agent (etanercept [Enbrel], Amgen Inc., Thousand Oaks, CA) with systemic corticosteroids for the management of IPS reported high response rates and improved overall survival [7,8,14]. Etanercept is a soluble dimeric binding protein consisting of 2 soluble p75 TNF receptors fused to the Fc portion of a type I immunoglobulin molecule.…”

TNF-Receptor Inhibitor Therapy for the Treatment of Children with Idiopathic Pneumonia Syndrome. A Joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521)

“…Response rates of 18 to 30%, with day 28 survival < 50% have been reported when patients were treated with high dose corticosteroids and supportive care measures. [1–3, 20] In our current study, treatment with systemic corticosteroids and etanercept resulted in complete response rates of 71%, with day 28 survival 89% and 1-year survival 63%. Three other pediatric studies have confirmed that IPS remains an important complication in children, with cumulative incidence rates ranging from 6.7% – 11.8% post-HCT in children.…”

“…Recent, limited institution, clinical trials using a soluble, dimeric, TNFα binding protein (etanercept, Enbrel®; Amgen, Thousand Oaks, CA), when given in combination with systemic corticosteroids have noted significant improvements in response rate and early survival for patients with IPS. [3, 6, 20] In collaboration with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) and Children’s Oncology Group (COG), we have conducted a multi-center, phase II trial to determine whether the addition of etanercept to standard treatment would improve outcomes for children with IPS.…”

Lung parenchyma-derived IL-6 promotes IL-17A–dependent acute lung injury after allogeneic stem cell transplantation

“…[30][31][32][33] These laboratory insights led to clinical trials using TNF inhibition to treat IPS, which has demonstrated encouraging responses. [34][35][36] A large, prospective, phase 2 study combining etanercept with corticosteroids for children with IPS reported high early response rates and a 1-year survival of 63%, which is superior to all previous IPS reports. 36 A recent phase 3 trial of corticosteroids with or without etanercept, did not demonstrate definitive effects of TNF inhibition on response or survival of patients with IPS above steroids alone.…”