SL-401 Improves Overall Response Rate for Blastic Plasmacytoid Dendritic Cell Neoplasm

SL-401, a targeted therapy directed to the interleukin-3 receptor CD123, was shown to improve overall response (ORR) and complete response (CR) rates in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to data presented at the 2016 ASCO Annual Meeting.

Naveen Pemmaraju, MD, from the University of Texas MD Anderson Cancer Center in Houston, Texas, presented early results from the lead-in phase of an ongoing phase II trial of SL-401 in patients with this rare disease.

“This rare disease has features of different hematologic cancers, but there is no standard therapy for BPDCN,” Dr. Pemmaraju said in an interview with ASH Clinical News, “and people are ‘borrowing’ therapies from acute lymphoid leukemia, acute myeloid leukemia, and lymphomas. There is an urgent need for more therapies for BPDCN patients.”

The multicenter, phase II trial was designed to assess the efficacy of SL-401 in patients with BPDCN and relapsed/refractory acute myeloid leukemia (AML) in two stages:

  • lead-in (stage 1): Patients received SL-401 as a daily intravenous infusion at 7, 9, 12, or 16 ug/kg for up to 5 doses, repeated every 21 days, to determine the maximum tolerated dose (MTD)
  • expansion (stage 2): Patients received SL-401 at the optimal stage 1 dose

Stage 1 is completed, and the expansion stage is ongoing. At the data cut-off point (January 20, 2016), 18 patients with BPDCN (9 in each stage) were enrolled in the trial and received SL-401 treatment: three patients received 7 ug/kg (n=3; all in stage 1), and 15 received 12 ug/kg (6 in stage 1; 9 in stage 2). The median patient age was 70 years (range = 45-82 years).

SL-401 12 ug/kg was the maximum tested/recommended dose for patients with BPDCN and the MTD in patients with relapsed/refractory AML; MTD was not reached in BPDCN.

Among the 15 evaluable BPDCN patients, 87 percent (n=13) responded. The ORR was 100 percent when SL-401 was used as front-line treatment (n=10/10) and 60 percent when it was used in the relapsed/refractory setting (n=3/5). Unlike most hematologic cancers, BPDCN affects the skin, as well as lymph nodes and bone marrow, Dr. Pemmaraju noted, and patients treated with SL-401 saw marked disease reductions in all three of these symptoms.

Of the eight previously untreated patients, SL-401 12 ug/kg 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.


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.