title: Combination Therapy with Inolimomab and Etanercept for Severe Steroid-Refractory Acute Graft-versus-Host Disease.
abstract: Steroid-refractory acute graft-versus-host disease (aGVHD) remains an important cause of morbidity and mortality after allogeneic stem cell transplantation (SCT). A protocol on the management of aGVHD was introduced in our center that incorporated a prospective study on combination therapy with inolimomab (anti-IL-2Rα) and etanercept (anti-tumor necrosis factor-α) for steroid-refractory aGVHD. We evaluated the efficacy and safety in 21 consecutively treated patients. The patients had developed refractory aGVHD after SCT (n = 16) or donor lymphocyte infusion (n = 5), and aGVHD was classified as severe in all patients, mostly due to gastrointestinal involvement stages 2 to 4. No drug-related side effects were observed apart from the infections expected to occur in these severely immunocompromised patients. Overall response at day 28 of second-line therapy was 48% (10/21), with 6 and 4 patients achieving a complete and partial response, respectively. Eventually, 19 patients died (90%), with early mortality (<6 months) predominantly resulting from refractory aGVHD and secondary infections and late mortality resulting from relapse of the underlying disease. With a median follow-up of 55 days, the estimated rates of 6-month and 2-year overall survival were dismal, 29% and 10%, respectively. In conclusion, the combination of inolimomab and etanercept for steroid-refractory aGVHD failed to improve the dismal prognosis of severe steroid-refractory aGVHD.
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Lenneke.vanGroningen@radboudumc.nl.
authors.forename: Lenneke F J
authors.initials: LF
authors.lastname: van Groningen
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Aleida M
authors.initials: AM
authors.lastname: Liefferink
authors.affiliation: Department for Health Evidence, Biostatistics, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Anton F J
authors.initials: AF
authors.lastname: de Haan
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Nicolaas P M
authors.initials: NP
authors.lastname: Schaap
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: J Peter
authors.initials: JP
authors.lastname: Donnelly
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Nicole M A
authors.initials: NM
authors.lastname: Blijlevens
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Walter J F M
authors.initials: WJ
authors.lastname: van der Velden
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018572:Disease-Free Survival; D004351:Drug Resistance / Q000187:drug effects*; D004359:Drug Therapy, Combination / Q000379:methods; D000068800:Etanercept / Q000008:administration & dosage*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D013256:Steroids / Q000008:administration & dosage; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D013256:Steroids; C079843:inolimomab; D000068800:Etanercept
keywords: Acute GVHD; Allogeneic stem cell transplantation; Etanercept; Inolimomab; Steroid refractory