PracticeUpdate: Haematology & Oncology

EHA 2016 19

SL-401 demonstrates robust activity against blastic plasmacytoid dendritic cell neoplasm SL-401 has demonstrated

N aveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center, Houston, explained that SL-401 is a novel targeted therapy directed to the interleukin-3 receptor. The interleukin-3 receptor is overexpressed by many haematologic cancers, including BPDCN, acute myeloid leukaemia, myeloproliferative neoplasms, and multiple myeloma. In a prior phase 1/2 trial, SL-401 demonstrated clinical activity, including multiple complete responses, in patients with BPDCN, a highly aggressive malignancy of unmet medical need and poor prognosis. Dr Pemmaraju and colleagues built on this prior experience and reported updated efficacy and safety data from their ongoing SL- 401 registration trial in BPDCN. This phase 2 trial is a single-arm, open-label, two-stage study consisting of a lead-in dose escalation (stage 1) and subsequent expansion stage (stage 2) designed to generate safety and efficacy data to support potential registration in BPDCN. In stage 1, patients with BPDCN or relapsed/ refractory acute myeloid leukaemia receive SL-401 as a daily intravenous infusion for up to 5 days (7, 9, 12, or 16 μg/kg daily) every 21 days. In stage 2, patients with BPDCN receive SL- 401 at the optimal stage 1 dose and schedule. Response criteria include skin assessment by modified severity weighted assessment tool, and bone marrow, lymph node, and viscera by standard measures. Clinical complete response is defined as no detectable disease in bone marrow, lymph nodes, or viscera, with microscopic-only skin disease. At data cutoff (1/20/16), 48 patients (18 BPDCN; 30 relapsed/refractory acute myeloid leukemia) were treated with SL-401. Eighteen BPDCN patients (9+ 9 in stages 1 and 2) received SL-401 (7 μg/kg, n=3 [stage 1]; 12 μg/kg, n=15 [6 + 9 in stages 1 and 2]). The median age was 70 years (range 45–82 and one compassionate use patient age 15 years). Data on 30 relapsed/refractory patients with acute myeloid leukaemia (14+16 in stages 1 and 2) will be reported separately. Most common treatment-related adverse events

(all grades) were transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 patients had capillary leak syndrome grade 5 (7 μg/kg) and grade 4 (12 μg/kg). Safety precautions were developed and successfully implemented to minimise risk of severe capillary leak syndrome. Since adoption, severe capillary leak syndrome has not been observed at doses up to 12 μg/kg. No cumulative side effects were observed over multiple cycles. In stage 1, 12 μg/kg was the maximum tested and recommended stage 2 dose for BPDCN and maximum tolerated in relapsed/refractory acute myeloid leukaemia. Maximum tolerated dose was not reached in BPDCN. An 87% (13/15) overall response rate was observed in 15 evaluable BPDCN patients, with marked disease reductions in skin, bone marrow, lymph node, and viscera. A 100% (10/10) objective response rate was observed in evaluable first-line BPDCN patients, with 90% (9/10) of patients achieving complete response (n=7) or clinical complete response (n=2). A 100% (8/8) objective response rate was observed in evaluable first-line BPDCN patients treated at the optimal dose (12 μg/kg), and all eight patients achieved either complete response (n=6) or clinical complete response (n=2). Six of the eight patients either remain on SL-401 in complete response (n=4; duration ongoing at 3+ to 8+ cycles) or were bridged to stem cell transplant (n=2; one complete response, one clinical complete response after seven and four cycles, respectively). Dr Pemmaraju concluded that SL-401 demonstrated robust single-agent activity in BPDCN, including 100% objective response rate in first-line, and 87% in all lines, with multiple complete responses in a phase 2 trial. Response duration data are maturing and encouraging. SL-401 is also being developed in additional interleukin-3 receptor/ CD123-positive haematologic malignancies, including acute myeloid leukaemia in complete response with minimal residual disease and high-risk myeloproliferative neoplasms.

robust single-agent activity in blastic plasmacytoid dendritic cell neoplasm (BPDCN), including a 100% objective response rate in first-line, and 87% in all lines.

DECEMBER 2016