led to complete responses ( CR ) in five patients and clinical CR ( defined as CR in bone marrow , peripheral blood , lymph nodes , and spleen / liver or skin with gross clearance of all lesions from baseline ) in three patients .
Six of those eight patients remain on SL-401 therapy while in remission ( n = 4 ) or were successfully bridged to hematopoietic cell transplantation ( n = 2 ).
The most common treatment-related adverse events ( AEs ) included transaminase elevation ( 57 %), which , Dr . Pemmaraju said , were “ transient and usually during the first treatment cycle .” Also , no patients on the study have required a dose reduction .
Two patients in stage 1 had capillary leak syndrome ( CLS ), occurring as a grade 5 AE at the 7 ug / kg dose and as a grade 4 AE at the 12 ug / kg dose . Since these findings , safety precautions have been implemented to minimize the risk of severe CLS , which has not occurred at doses up to 12 ug / kg since the new precautions were implemented , according to the authors .
“ SL-401 demonstrated robust single-agent activity in BPDCN , including 100 percent ORR in first-line , and 87 percent in all-lines , with multiple CRs ,” Dr . Pemmaraju and authors concluded , however , results from this small study will need to be tested in larger patient populations . Response duration data are maturing , and results of SL-401 in the 30 patients with relapsed / refractory AML will be reported separately , they added .
Reference
Pemmaraju N , Lane AA , Sweet KL , et al . Results from phase 2 registration trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm ( BPDCN ): Lead-in completed , expansion stage ongoing . Abstract # 7006 . Presented at the 2016 American Society of Clinical Oncology Annual Meeting , June 4 , 2016 ; Chicago , IL .
Real-World Study Suggests Acquired Hemophilia A Patients Can Receive Lower Doses of Recombinant Porcine Factor VIII Than Recommended
A retrospective study presented at the Thrombosis and Hemostasis Societies of North America 2016 Summit provided real-world data on recombinant porcine factor VIII ( rpFVIII ) for patients with acquired hemophilia A that suggests that a lower dose of the drug than previously recommended by the FDA still leads to effective bleeding control .
In the clinical trial that served as the basis for rpFVIII ’ s approval , a primary major adverse event ( AE ) was the development of anti-porcine FVIII antibodies . However , the results lack generalizability to the real-world patient population due to very specific eligibility criteria , according to Michael Tarantino , MD , lead author of one of the studies presented at this year ’ s Summit .
To characterize the real-world experience with rpFVIII , Dr . Tarantino , of the Bleeding & Clotting Disorders Institute in Peoria , Illinois , and colleagues conducted a chart review of seven patients with acquired hemophilia A who received rpFVIII at one of four institutions .
Five of the patients treated with rpFVIII for major bleeding achieved good hemostatic efficacy , meaning they required one or two infusions more than estimated to control a bleeding episode . Bleeding ceased within 24 hours in four patients , while another patient ’ s bleeding ceased within four days . The majority of patients also had no bleeding recurrences .
Three patients developed anti-porcine antibodies , which resulted in one patient withdrawing from treatment . No other rpFVIIIrelated AEs were reported . During follow-up :
• four patients survived with inhibitor eradication
• two patients died with inhibitors present
• one patient was discharged and died due to unrelated causes 4.5 months later
Notably , the researchers found that patients benefited from a substantially lower dose of rpFVIII than the recommended U . S . FDA dose ( initial dose of 200 U / kg followed by maintenance dosing titrated according to bleeding control and trough FVIII activity levels ). In the study by Dr . Tarantino and colleagues , an rpFVIII loading dose of 100 U / kg ( n = 6 ) or 200 U / kg ( n = 1 ) resulted in increased FVIII activity ( from < 1 – 9 % to 109 – 650 %, within 0.25 – 7 hours post-dose ) in all but one patient .
Subsequent median doses ranged from 30 U / kg to 200 U / kg and were administered at intervals ranging from six to 48 hours .
“ The doses of rpFVIII used were substantially less than in the registration study ,” Dr . Tarantino and colleagues concluded . “ The ability to titrate rpFVIII dose using FVIII activity was considered advantageous , particularly where this allowed a dose reduction over time .” However , the considerable delay observed in the diagnosis of acquired hemophilia may have affected treatment effectiveness in some cases , thus limiting the efficacy of the study outcomes .
Reference
Tarantino M , Cuker A , Hardesty B , et al . Practical clinical experience with recombinant porcine FVIII for acquired hemophilia A . Abstract # 44 . Presented at the 3rd Annual Summit of the Thrombosis & Hemostasis Societies of North America , April 15 , 2016 ; Chicago , IL .
For another take on this issue , turn to “ Drawing First Blood : Choosing Between Treatment Strategies for Patients With Acquired Hemophilia A ” on page 43 in the October issue . We asked Rebecca Kruse-Jarres , MD , MPH , and ASH Clinical News Associate Editor Alice Ma , MD , to debate the merits of newer FVIII replacement products and standard bypassing agents .
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