title: DAS181 for Treatment of Parainfluenza Virus Infections in Hematopoietic Stem Cell Transplant Recipients at a Single Center.
abstract: Parainfluenza virus (PIV) causes severe respiratory infections in hematopoietic stem cell transplant (HSCT) recipients. Currently, no effective therapies are available. DAS181 is a novel antiviral agent that inhibits attachment of PIV to respiratory cells, but clinical data on the use of DAS181 for PIV infection are limited to case reports. We report the clinical manifestations and outcomes of 16 HSCT recipients who received DAS181 daily for the treatment of PIV infection through a compassionate-use protocol or a single-arm clinical trial. Of the 16 patients (clinical trial: 9; compassionate use: 7), 13 were allogeneic HSCT recipients and 8 had graft-versus-host disease. PIV types were 3 (n = 7), 4 (n = 5), 1 (n = 3), and type 3 and 4 coinfection (n = 1). Fourteen patients had pneumonia. All patients presented with cough, 14 had dyspnea, 11 had hypoxia, and 8 had a fever. Patients received 5 to 10 days of treatment. Nine patients (56%) had a complete clinical response after DAS181 therapy and 4 (25%) had a partial response. The 3 patients without a clinical response had coinfections with other pathogens. Of the 7 patients with virologic and spirometric data, 5 had >1-log reduction in nasopharyngeal swab PIV viral load and 4 had improved forced expiratory volumes by the end of treatment. Three patients (19%) died within 30 days and 2 of these deaths were related to PIV infection. Our data suggest that DAS181 may be an effective therapy for PIV pneumonia in HSCT recipients. Randomized placebo-controlled trials are needed to better evaluate its efficacy.
authors.affiliation: Department of Medicine, Weill Cornell Medicine, New York, New York. Electronic address: mis2053@med.cornell.edu.
authors.forename: Mirella
authors.initials: M
authors.lastname: Salvatore
authors.affiliation: Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Satlin
authors.affiliation: Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Jacobs
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Jenkins
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Audrey N
authors.initials: AN
authors.lastname: Schuetz
authors.affiliation: Ansun Pharmaceuticals, Ansun BioPharma, San Diego, California.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Moss
authors.affiliation: Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Besien
authors.affiliation: Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Tsiporah
authors.initials: T
authors.lastname: Shore
authors.affiliation: Department of Medicine, Weill Cornell Medicine, New York, New York.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Soave
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018184:Paramyxoviridae Infections / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D011024:Pneumonia, Viral / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D018108:Respirovirus; D019562:Viral Load
chemical_list: D011993:Recombinant Fusion Proteins; C525612:oplunofusp
keywords: DAS181; Hematopoietic stem cell transplant; Parainfluenza virus; Pneumonia