Background: sALCL is a CD30-expressing malignancy comprising ~2-3% of all NHL cases. Brentuximab vedotin consists of an anti-CD30 antibody conjugated by a plasma-stable linker to the potent antimicrotubule agent, monomethyl auristatin E (MMAE). Brentuximab vedotin selectively induces apoptotic death of CD30+ cells by binding, internalizing, and releasing MMAE. Methods: A phase II, single-arm, multicenter study evaluated the efficacy and safety of brentuximab vedotin in patients (pts) with relapsed or refractory sALCL. Pts received brentuximab vedotin 1.8 mg/kg q3 weeks (wks) as a 30‑minute outpatient IV infusion for up to 16 cycles. The primary endpoint was the objective response rate (ORR) per an independent review facility (IRF) according to Cheson 2007. Results: 58 pts were enrolled; 57% were male, median age was 52 yrs (range 14–76 yrs). 72% of pts had ALK negative sALCL. Pts had received a median of 2 (range 1–6) prior systemic therapies. 62% of pts had primary refractory disease, 50% were refractory to their most recent prior therapy, and 22% had never responded to any prior therapy. At the time of primary efficacy analysis, ORR per IRF was 86% (50 of 58 pts) with CRs in 53% of pts (31 of 58). Median duration of objective response had not yet been reached; the duration ranged from 0.3 to 45.3 wks. Of 15 pts with malignant cutaneous lesions at baseline, 14 (93%) had resolution of all lesions; median time to resolution was 4.9 wks. After achieving a remission with brentuximab vedotin, 7 pts received an allogeneic stem cell transplant (SCT) and 7 pts had an autologous SCT. Treatment-related adverse events (AEs) of any grade in ≥15% of pts were peripheral sensory neuropathy (36%), nausea (24%), fatigue (22%), diarrhea (19%), and neutropenia (17%). AEs ≥ Grade 3 in ≥10% of patients were neutropenia (21%); thrombocytopenia (14%), and peripheral sensory neuropathy (10%). No treatment-related Grade 5 events were observed. Conclusions: Brentuximab vedotin induced objective responses in 86% of pts with highly refractory sALCL, including a high proportion of CRs, with manageable AEs. Updated response durability and safety will be presented at the meeting.