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.
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U2 - 10.1182/blood-2014-04-566737
DO - 10.1182/blood-2014-04-566737
M3 - Article
C2 - 24859366
AN - SCOPUS:84904465235
SN - 0006-4971
VL - 124
SP - 385
EP - 392
JO - Blood
JF - Blood
IS - 3
ER -