On Location
Conference Coverage
ADVANCES ACROSS HEMATOLOGY
his month , we conclude our coverage of the European Hematology Association ’ s 23rd Congress , which was held June 14-17 in Stockholm , Sweden , where more than 10,000 international hematologists met to share emerging results from clinical and translational research in hematologic disorders and discuss the latest evidence-based approaches to their diagnosis and management .
Here , ASH Clinical News presents highlights from the meeting , including new options for blastic plasmacytoid dendritic cell neoplasm and chronic lymphocytic leukemia .
Tagraxofusp : A New Option for Blastic Plasmacytoid Dendritic Cell Neoplasm ?
Attendees browse posters at the 23rd EHA Congress .
Treatment with tagraxofusp , an anti-CD123 targeted agent previously known as SL-401 , appeared to be safe and effective for managing blastic plasmacytoid dendritic cell neoplasm ( BPDCN ), according to results from a phase II trial presented at the 23rd Congress of the European Hematology Association .
“ This disease , with a median overall survival ( OS ) of eight to 14 months , historically , has no approved standard therapies available ,” according to lead study author Naveen Pemmaraju , MD , of The University of Texas MD Anderson Cancer Center in Houston . The results reported with tagraxofusp in this trial are encouraging , he added , especially considering “ the side-effect profile we observed , and keeping in mind our patients with BPDCN are at a median age of 70 or older and may not be candidates for intensive chemotherapy .”
The multicenter , open-label , non-randomized trial included 42 patients with either treatment-naïve or relapsed / refractory BPDCN . Patients received tagraxofusp as a daily intravenous infusion of 7 mcg / kg / day ,
9 mcg / kg / day , or 12 mcg / kg / day on days one through five of a 21-day treatment cycle . Sixteen patients with either previously untreated or relapsed / refractory disease were included in stage 1 ( lead-in ) of the trial . Stage 2 ( expansion ) included 13 patients with either type of disease and stage 3 ( pivotal , confirmatory ) included 16 patients with treatment-naïve disease ; these patients received tagraxofusp 12 mcg / kg , the optimal dose determined in stage 1 .
The most common treatment-related adverse events ( AEs ) reported across the entire patient population were :
• transaminitis ( 52 %)
TABLE 1 . Efficacy Outcomes of Tagraxofusp 12 mcg / kg
• hypoalbuminemia ( 50 %)
• thrombocytopenia ( 38 %)
Disease Status Treatment-Naïve BPDCN Relapsed / Refractory BPDCN n 29 13 ORR , n (%) 26 ( 90 %) 9 ( 69 %) CR / CRc / CRi , n (%) 21 ( 72 %) 5 ( 38 %) CR 12 1 CRc 7 3 CRi 2 1 PR , n (%) 5 ( 17 %) 4 ( 31 %) Bridged to transplant , n (%) 13 ( 45 %) 1 ( 8 %)
ORR = overall response rate ; CR = complete response ; CRc = clinical CR ( absence of gross disease with minimal residual skin abnormality ); CRi = CR with incomplete hematologic recovery ; PR = partial response
Eight patients ( 19 %) experienced capillary leak syndrome at the highest treatment dose , though the authors noted that this was “ generally manageable and reversible .”
Most ( 90 percent ) of patients with treatmentnaïve disease ( n = 26 / 29 ) responded to treatment with tagraxofusp 12 mcg / kg , Dr . Pemmaraju reported ( TABLE
1 ). This included 21 patients who achieved a combined endpoint of complete response ( CR ), clinical CR ( CRc ; absence of gross disease with minimal residual skin abnormality ), or CR with incomplete hematologic recovery ( CRi ).
Stage 3 of this trial met its primary endpoint , with a CR / CRc rate of 54 percent .
The authors also noted that median OS was not reached in treatment-naïve patients .
Based on these results , the manufacturers submitted a biologics license application for tagraxofusp to the U . S . Food and Drug Administration . Tagraxofusp also is being evaluated as a single agent or in combination with other agents for the treatment of chronic myelomonocytic leukemia , high-risk myelodysplastic syndromes , acute myeloid leukemia , multiple myeloma , and myelofibrosis .
The study is limited by its small population , lack of a comparator arm , and lack of data on response duration . However , Dr . Pemmaraju said , “ the encouraging single-agent activity seen here is notable . As is the case with many of our treatments in leukemia , the next era of research in BPDCN will need to focus on combinations , such as with hypomethylating agents , cytotoxic chemotherapy , BCL2 inhibitors , and other targeted agents .” He added that more research is needed into “ the timing and various modalities of hematopoietic cell transplantation for patients with BPDCN , especially in the era of new targeted agents being investigated .”
The researchers reported no financial conflicts .
REFERENCE
Pemmaraju N , Sweet K , Lane A , et al . Results of pivotal phase 2 trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm . Abstract # S116 . Presented at the 23rd Congress of the European Hematology Association , June 15 , 2018 ; Stockholm , Sweden .
42 ASH Clinical News September 2018