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: 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
• Journal: Blood (Blood) Vol. 124 Issue 3 Pg. 385-92 (Jul 17 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24859366 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• Diphtheria Toxin
• IL3 protein, human
• Interleukin-3
• Receptors, Interleukin-3
• Recombinant Fusion Proteins
• tagraxofusp

Topics

• Adult
• Aged
• Dendritic Cells (immunology, pathology)
• Diphtheria Toxin (administration & dosage, adverse effects, therapeutic use)
• Hematologic Neoplasms (immunology, pathology, therapy)
• Humans
• Interleukin-3 (administration & dosage, adverse effects, therapeutic use)
• Male
• Molecular Targeted Therapy
• Prospective Studies
• Receptors, Interleukin-3 (antagonists & inhibitors)
• Recombinant Fusion Proteins (administration & dosage, adverse effects, therapeutic use)
• Skin Neoplasms (immunology, pathology, therapy)
• Treatment Outcome