Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients

Arthur E. Frankel, Jung H. Woo, Chul Ahn, Naveen Pemmaraju, Bruno C. Medeiros, Hetty E. Carraway, Olga Frankfurt, Stephen J. Forman, Xuezhong A. Yang, Marina Konopleva, Francine Garnache-Ottou, Fanny Angelot-Delettre, Christopher Brooks, Michael Szarek, Eric Rowinsky

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

This is the first prospective study of treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologicmalignancy 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 inBPDCNpatients 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 1 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.

Original languageEnglish (US)
Pages (from-to)385-392
Number of pages8
JournalBlood
Volume124
Issue number3
DOIs
StatePublished - Jul 17 2014

Fingerprint

Interleukin-3 Receptors
Dendritic Cells
Neoplasms
Therapeutics
Recurrence
Hypoalbuminemia
Chills
Chemotherapy
Combination Drug Therapy
Thrombocytopenia
Hypotension
Edema
Catalytic Domain
Skin
Appointments and Schedules
Leukemia
Fever
Prospective Studies

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. / Frankel, Arthur E.; Woo, Jung H.; Ahn, Chul; Pemmaraju, Naveen; Medeiros, Bruno C.; Carraway, Hetty E.; Frankfurt, Olga; Forman, Stephen J.; Yang, Xuezhong A.; Konopleva, Marina; Garnache-Ottou, Francine; Angelot-Delettre, Fanny; Brooks, Christopher; Szarek, Michael; Rowinsky, Eric.

In: Blood, Vol. 124, No. 3, 17.07.2014, p. 385-392.

Research output: Contribution to journalArticle

Frankel, AE, Woo, JH, Ahn, C, Pemmaraju, N, Medeiros, BC, Carraway, HE, Frankfurt, O, Forman, SJ, Yang, XA, Konopleva, M, Garnache-Ottou, F, Angelot-Delettre, F, Brooks, C, Szarek, M & Rowinsky, E 2014, 'Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients', Blood, vol. 124, no. 3, pp. 385-392. https://doi.org/10.1182/blood-2014-04-566737
Frankel, Arthur E. ; Woo, Jung H. ; Ahn, Chul ; Pemmaraju, Naveen ; Medeiros, Bruno C. ; Carraway, Hetty E. ; Frankfurt, Olga ; Forman, Stephen J. ; Yang, Xuezhong A. ; Konopleva, Marina ; Garnache-Ottou, Francine ; Angelot-Delettre, Fanny ; Brooks, Christopher ; Szarek, Michael ; Rowinsky, Eric. / Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients. In: Blood. 2014 ; Vol. 124, No. 3. pp. 385-392.
@article{b6f5d799435b4d228894270e089afe5d,
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 hematologicmalignancy 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 inBPDCNpatients 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 1 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.",
author = "Frankel, {Arthur E.} and Woo, {Jung H.} and Chul Ahn and Naveen Pemmaraju and Medeiros, {Bruno C.} and Carraway, {Hetty E.} and Olga Frankfurt and Forman, {Stephen J.} and Yang, {Xuezhong A.} and Marina Konopleva and Francine Garnache-Ottou and Fanny Angelot-Delettre and Christopher Brooks and Michael Szarek and Eric Rowinsky",
year = "2014",
month = "7",
day = "17",
doi = "10.1182/blood-2014-04-566737",
language = "English (US)",
volume = "124",
pages = "385--392",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "3",

}

TY - JOUR

T1 - Activity of SL-401, a targeted therapy directed to interleukin-3 receptor, in blastic plasmacytoid dendritic cell neoplasm patients

AU - Frankel, Arthur E.

AU - Woo, Jung H.

AU - Ahn, Chul

AU - Pemmaraju, Naveen

AU - Medeiros, Bruno C.

AU - Carraway, Hetty E.

AU - Frankfurt, Olga

AU - Forman, Stephen J.

AU - Yang, Xuezhong A.

AU - Konopleva, Marina

AU - Garnache-Ottou, Francine

AU - Angelot-Delettre, Fanny

AU - Brooks, Christopher

AU - Szarek, Michael

AU - Rowinsky, Eric

PY - 2014/7/17

Y1 - 2014/7/17

N2 - This is the first prospective study of treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologicmalignancy 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 inBPDCNpatients 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 1 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.

AB - This is the first prospective study of treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologicmalignancy 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 inBPDCNpatients 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 1 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.

UR - http://www.scopus.com/inward/record.url?scp=84904465235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904465235&partnerID=8YFLogxK

U2 - 10.1182/blood-2014-04-566737

DO - 10.1182/blood-2014-04-566737

M3 - Article

VL - 124

SP - 385

EP - 392

JO - Blood

JF - Blood

SN - 0006-4971

IS - 3

ER -