Complete Remissions with Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma

Abstract Abstract 961 Background: Systemic anaplastic large cell lymphoma (sALCL) is a CD30-expressing malignancy comprising approximately 2–3% of all cases of non-Hodgkin lymphoma. The antibody-drug conjugate (ADC) brentuximab vedotin (SGN-35) delivers the highly potent antimicrotubule agent monomethyl auristatin E (MMAE) to CD30-positive malignant cells by binding specifically to CD30 on the cell surface and releasing MMAE inside the cell via lysosomal degradation. Binding of MMAE to tubulin disrupts the microtubule network within the cell, induces cell cycle arrest, and results in apoptotic death of the CD30-expressing tumor cell. In phase 1 studies, brentuximab vedotin demonstrated good tolerability and notable antitumor activity in patients with relapsed or refractory sALCL: 6 of 7 treated patients achieved complete remissions (CR). Methods: A phase 2, single-arm, multicenter study was conducted to evaluate the efficacy and safety of brentuximab vedotin in patients with relapsed or refractory sALCL. Brentuximab vedotin 1.8 mg/kg was administered every 3 weeks as a 30-minute outpatient IV infusion for up to 16 cycles of treatment. Determination of antitumor efficacy was based on objective response assessments according to the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Results: A total of 58 patients were treated in this study; interim data are presented for the first 30 treated patients. 53% of patients were female and median age was 55 years (range 14–71). The majority of patients had ALK-1 negative tumor (70%, or n=21) and 4 patients (13%) had bone marrow involvement at baseline. The median number of prior chemotherapy regimens was 2 (range 1–6) and 8 patients (27%) had failed previous autologous hematopoietic stem cell transplant (SCT). 19 patients (63%) had primary refractory disease, and 16 patients (53%) had not responded to the most recent prior therapy. The objective response rate (ORR) by investigator assessment was 87%; 57% of patients achieved a CR (n=17) and 30% of patients achieved a partial remission (PR; n=9). The remaining patients had stable disease (n=3) or were not evaluable for response (n=1). Similar proportions of ALK-1 negative and ALK-1 positive patients achieved CR and PR. Reduction in tumor burden was observed in 97% of patients. The median time to objective response was 6 weeks (range 5–12) and the duration of objective responses currently range from 4–36 weeks, with responses ongoing in 18 patients. B symptoms resolved in 9 of 10 patients (90%) who had these symptoms at baseline. After achieving a CR with brentuximab vedotin, 10 patients (33%) went on to receive an autologous or allogeneic SCT. The most common (>20%) adverse events (AEs) of any grade were nausea (47%), diarrhea (40%), peripheral sensory neuropathy (40%), pyrexia (33%), dyspnea (30%), fatigue (27%), insomnia (23%), and neutropenia (23%). Grade 3/4 AEs considered related to brentuximab vedotin observed in >1 patient were neutropenia (17%), peripheral sensory neuropathy (13%), diarrhea (7%), and anemia (7%); no treatment-related Grade 5 events were observed. 7 patients (23%) discontinued treatment due to an AE. Conclusion: In this interim analysis of 30 patients with relapsed or refractory sALCL, the investigator-assessed ORR was 87% and the CR rate was 57%. Brentuximab vedotin treatment was associated with manageable AEs; the most common in the study were nausea, diarrhea, and peripheral sensory neuropathy. The rate of complete remissions observed thus far in this study with single-agent treatment suggests that brentuximab vedotin has potential for the treatment of sALCL. Results of the independent assessment of response for all patients, duration of response, progression-free survival, and updated safety data will be presented at the meeting. Disclosures: Shustov: Seattle Genetics, Inc.: Research Funding, Steering Committee member. Off Label Use: The clinical trial uses an investigational drug, brentuximab vedotin (SGN-35). Advani:Seattle Genetics, Inc.: Research Funding. Brice:Seattle Genetics, Inc.: Research Funding. Bartlett:Seattle Genetics, Inc.: Research Funding. Rosenblatt:Seattle Genetics, Inc.: Research Funding. Illidge:Seattle Genetics, Inc.: Research Funding; Roche: Consultancy; Biogen Idec: Consultancy; Amgen: Consultancy. Matous:Seattle Genetics, Inc.: Research Funding; Celgene: Honoraria, Speakers Bureau; Millennium: Speakers Bureau; Cephalon: Speakers Bureau. Ramchandren:Seattle Genetics, Inc.: Research Funding. Fanale:Seattle Genetics, Inc.: Research Funding. Connors:Seattle Genetics, Inc.: Research Funding. Yang:Seattle Genetics, Inc.: Employment. Sievers:Seattle Genetics, Inc.: Employment, Equity Ownership. Kennedy:Seattle Genetics, Inc.: Employment, Equity Ownership. Pro:Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding.

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