title: Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients.
abstract: This is the first prospective study of treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy derived from plasmacytoid dendritic cells that typically involves the skin and rapidly progresses to a leukemia phase. Despite being initially responsive to intensive combination chemotherapy, most patients relapse and succumb to their disease. Because BPDCN blasts overexpress the interleukin-3 receptor (IL3R), the activity of SL-401, diptheria toxin (DT)388IL3 composed of the catalytic and translocation domains of DT fused to IL3, was evaluated in BPDCN patients in a phase 1-2 study. Eleven patients were treated with a single course of SL-401 at 12.5 μg/kg intravenously over 15 minutes daily for up to 5 doses; 3 patients who had initial responses to SL-401 received a second course in relapse. The most common adverse events including fever, chills, hypotension, edema, hypoalbuminemia, thrombocytopenia, and transaminasemia were transient. Seven of 9 evaluable (78%) BPDCN patients had major responses including 5 complete responses and 2 partial responses after a single course of SL-401. The median duration of responses was 5 months (range, 1-20+ months). Further studies of SL-401 in BPDCN including those involving multiple sequential courses, alternate schedules, and combinations with other therapeutics are warranted. This trial is registered at clinicaltrials.gov as #NCT00397579.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX;
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Frankel
authors.affiliation: Baylor Scott & White Health, Temple, TX;
authors.forename: Jung H
authors.initials: JH
authors.lastname: Woo
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX;
authors.forename: Chul
authors.initials: C
authors.lastname: Ahn
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Stanford University School of Medicine, Stanford, CA;
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.affiliation: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH;
authors.forename: Hetty E
authors.initials: HE
authors.lastname: Carraway
authors.affiliation: Northwestern University Feinberg School of Medicine, Chicago, IL;
authors.forename: Olga
authors.initials: O
authors.lastname: Frankfurt
authors.affiliation: City of Hope, Duarte, CA;
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Bon Secours St. Francis Health Systems, Greenville, SC;
authors.forename: Xuezhong A
authors.initials: XA
authors.lastname: Yang
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX;
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: EFS Bourgogne Franche-Comte, INSERM UMR1098, EFS Bourgogne Franche-Comte, Besancon, France; and.
authors.forename: Francine
authors.initials: F
authors.lastname: Garnache-Ottou
authors.affiliation: EFS Bourgogne Franche-Comte, INSERM UMR1098, EFS Bourgogne Franche-Comte, Besancon, France; and.
authors.forename: Fanny
authors.initials: F
authors.lastname: Angelot-Delettre
authors.affiliation: Stemline Therapeutics, Inc., New York, NY.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brooks
authors.affiliation: Stemline Therapeutics, Inc., New York, NY.
authors.forename: Michael
authors.initials: M
authors.lastname: Szarek
authors.affiliation: Stemline Therapeutics, Inc., New York, NY.
authors.forename: Eric
authors.initials: E
authors.lastname: Rowinsky
mesh_terms: D000328:Adult; D000368:Aged; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007377:Interleukin-3 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D058990:Molecular Targeted Therapy; D011446:Prospective Studies; D016185:Receptors, Interleukin-3 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D004167:Diphtheria Toxin; C508596:IL3 protein, human; D007377:Interleukin-3; D016185:Receptors, Interleukin-3; D011993:Recombinant Fusion Proteins; C000592123:tagraxofusp