SL-401 is a novel targeted therapy, comprised of recombinant IL-3 genetically fused to a truncated diphtheria toxin payload, directed to the interleukin-3 receptor α (CD123), a target highly expressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN). SL-401 has been granted breakthrough therapy designation (BTD) for the treatment of patients with BPDCN. BPDCN is an aggressive hematologic malignancy with poor outcomes, including ~12 month overall survival (OS) from diagnosis, and no approved therapies or standard of care, highlighting the need for novel therapeutic approaches. Detailed results from the pivotal Phase 2 trial of SL-401 in BPDCN will be presented for the first time.


This pivotal Phase 2 trial of SL-401 is a multicenter, open label, non-randomized, single-arm trial. In Stage 1, first line (1L) and relapsed/refractory (r/r) BPDCN patients received SL-401 as a daily IV infusion at 7, 9, or 12 mcg/kg/day on days 1-5 of a 21-day cycle. Patients with BPDCN enrolled in subsequent stages received SL-401 at the dose determined in Stage 1 (12mcg/kg). Stage 2 enrolled 1L and r/r BPDCN patients, and Stage 3 enrolled only 1L BPDCN patients. Stage 3 was prospectively designed with a pre-specified analysis plan to support potential registration. Enrollment in Stages 1-3 has been completed. To ensure ongoing patient access, a Stage 4 cohort is currently open for enrollment of both 1L and r/r BPDCN patients.


45 patients with BPDCN (Stages 1 and 2: n=32; Stage 3: n=13) were enrolled at 7 sites in the US. The following results are from Stages 1 and 2; Stage 3 data will be presented at the conference. Median age was 72 years (range, 29-85 years); 81% were male. In Stage 1, 12 mcg/kg was the highest tested dose for BPDCN; MTD was not reached. Across all patients and doses, there was an 84% (27/32) overall response rate (ORR), and 59% (19/32) rate of complete response (CR), which includes CR with incomplete hematologic recovery (CRi) (n=1) and clinical CR (CRc; CR with minimal residual skin abnormality) (n=4). ORR was 95% (18/19), with a CR rate of 79% (15/19), in 1L patients. In r/r patients, ORR was 69% (9/13) with a 31% (4/13) CR rate. Eight patients with BPDCN (28%: 8/29) were bridged to stem cell transplant (SCT) following remission with SL-401 (12 mcg/kg), including 1 r/r patient; no cases of post-SCT veno-occlusive disease (VOD) have been reported in these patients. In first-line patients (SL-401: 12 mcg/kg), median OS has not been reached; PFS: 9.5 months. In r/r patients, median OS was 8.5 months; PFS: 3.6 months. Median follow-up was 4.5 months (range 0.5 to 22.9).

The most common treatment-related adverse events (TRAEs) with SL-401 across BPDCN and other indications (acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and multiple myeloma) (n=134 patients) were hypoalbuminemia (43%), transaminitis (43%), and thrombocytopenia (26%). Capillary leak syndrome (CLS), a well-documented side effect, occurred in 18% (24/134) of patients, and has been generally manageable and reversible; 2.2% (3/134) of cases resulted in deaths.


SL-401 continues to demonstrate notable single agent activity, including multiple CRs, in Stages 1 and 2 of the pivotal Phase 2 BPDCN trial. In 1L patients (SL-401: 12 mcg/kg), 44% (7/16) were bridged to SCT after a durable response from SL-401, and median OS has not been reached. SL-401 side effect profile has remained generally consistent and manageable over increased patient exposure and experience. Analysis of Stage 3 data is ongoing and detailed pivotal efficacy data from this cohort, along with updated Stage 1 and 2 results, will be presented at the conference for the first time.


Pemmaraju: LFB: Consultancy, Honoraria; Incyte Corporation: Consultancy, Honoraria; stemline: Consultancy, Honoraria, Research Funding; novartis: Consultancy, Honoraria, Research Funding; cellectis: Research Funding; affymetrix: Research Funding; roche diagnostics: Consultancy, Honoraria; abbvie: Research Funding. Lane: Stemline Therapeutics: Research Funding; N-of-one: Consultancy. Stein: Stemline: Consultancy; Amgen: Consultancy, Speakers Bureau. Vasu: Stemline Therapeutics: Research Funding; Boehringer-Ingelheim: Research Funding. Rizzieri: Erytech: Research Funding; Shire: Research Funding. Duvic: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Membership on an entity's Board of Directors or advisory committees, Other: Research funding (paid to institution); . Shubert: Stemline Therapeutics: Employment. Spence: Stemline Therapeutics: Consultancy. Shemesh: Stemline Therapeutics: Employment. Chen: Stemline Therapeutics: Employment. Brooks: Stemline Therapeutics: Employment, Equity Ownership, Patents & Royalties. Bergstein: Stemline Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. McDonald: Stemline Therapeutics: Employment, Equity Ownership. Goswami: Stemline Therapeutics: Employment. Sloan: Stemline Pharmaceuticals: Consultancy; Molecular Templates, Inc.: Consultancy. Lancet: Biopath, Biosight, Boehringer Ingelheim, Celator/Jazz, Celgene, Janssen, Karyopharm Therapeutics, and Novartis: Consultancy; Pfizer: Other: Institutional research funding. Kantarjian: Pfizer: Research Funding; Amgen: Research Funding; Bristol-Meyers Squibb: Research Funding; ARIAD: Research Funding; Novartis: Research Funding; Delta-Fly Pharma: Research Funding.

Author notes


Asterisk with author names denotes non-ASH members.

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