• Naveen Pemmaraju, Andrew A Lane, Kendra L Sweet, Anthony S Stein, Sumithira Vasu, William Blum, David A Rizzieri, Eunice S Wang, Madeleine Duvic, J Mark Sloan, Sharon Spence, Shay Shemesh, Christopher L Brooks, John Balser, Ivan Bergstein, Jeffrey E Lancet, Hagop M Kantarjian, and Marina Konopleva.
• From the University of Texas M.D. Anderson Cancer Center, Houston (N.P., M.D., H.M.K., M.K.); Dana-Farber Cancer Institute (A.A.L.) and Boston University School of Medicine (J.M.S.), Boston, and Veristat, Southborough (J.B.) - all in Massachusetts; H. Lee Moffitt Cancer Center, Tampa, FL (K.L.S., J.E.L.); City of Hope National Medical Center, Duarte, CA (A.S.S.); Ohio State University, Columbus (S.V.); Winship Cancer Institute of Emory University, Atlanta (W.B.); Duke University Medical Center, Durham, NC (D.A.R.); and Roswell Park Comprehensive Cancer Center, Buffalo (E.S.W.), and Stemline Therapeutics, New York (S. Spence, S. Shemesh, C.L.B., I.B.) - both in New York.
• N. Engl. J. Med. 2019 Apr 25; 380 (17): 162816371628-1637.

BackgroundBlastic plasmacytoid dendritic-cell neoplasm (BPDCN) is an aggressive hematologic cancer that is caused by transformed plasmacytoid dendritic cells that overexpress interleukin-3 receptor subunit alpha (IL3RA or CD123). Tagraxofusp (SL-401) is a CD123-directed cytotoxin consisting of human interleukin-3 fused to truncated diphtheria toxin.MethodsIn this open-label, multicohort study, we assigned 47 patients with untreated or relapsed BPDCN to receive an intravenous infusion of tagraxofusp at a dose of 7 μg or 12 μg per kilogram of body weight on days 1 to 5 of each 21-day cycle. Treatment continued until disease progression or unacceptable toxic effects. The primary outcome was the combined rate of complete response and clinical complete response among patients who had not received previous treatment for BPDCN. A secondary outcome was the duration of response.ResultsOf the 47 patients, 32 were receiving tagraxofusp as first-line treatment and 15 had received previous treatment. The median age of the patients was 70 years (range, 22 to 84). Among the 29 previously untreated patients who received tagraxofusp at a dose of 12 μg per kilogram, the primary outcome occurred in 21 (72%), and the overall response rate was 90%; of these patients, 45% went on to undergo stem-cell transplantation. Survival rates at 18 and 24 months were 59% and 52%, respectively. Among the 15 previously treated patients, the response rate was 67%, and the median overall survival was 8.5 months. The most common adverse events were increased levels of alanine aminotransferase (64%) and aspartate aminotransferase (60%), hypoalbuminemia (55%), peripheral edema (51%), and thrombocytopenia (49%). Capillary leak syndrome was reported in 19% of the patients and was associated with one death in each of the dose subgroups.ConclusionsIn adult patients with untreated or relapsed BPDCN, the use of tagraxofusp led to clinical responses. Serious adverse events included capillary leak syndrome; hepatic dysfunction and thrombocytopenia were common. (Funded by Stemline Therapeutics and the Leukemia and Lymphoma Society Therapy Acceleration Program; ClinicalTrials.gov number, NCT02113982.).Copyright © 2019 Massachusetts Medical Society.

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