1063O - Sequential Therapy with Brentuximab Vedotin in Newly Diagnosed Patients with Systemic Anaplastic Large Cell Lymphoma

Abstract

ABSTRACT Brentuximab vedotin (ADCETRIS®) comprises an anti-CD30 antibody conjugated by a protease-cleavable linker to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). In a pivotal phase 2 study in patients (pts) with relapsed/refractory systemic anaplastic large cell lymphoma (sALCL), objective response rate was 86% and median duration of response was 12.6 months. A phase 1, open-label, multicenter study was implemented to determine the safety and activity of sequential and combination treatment approaches of brentuximab vedotin with CHOP or CH-P chemotherapy in newly diagnosed pts with CD30-positive mature T- and NK-cell lymphomas (ClinicalTrials.gov NCT01309789). This abstract presents data from Arm 1 of the study, which employs sequential treatment in sALCL pts. Single-agent brentuximab vedotin (1.8 mg/kg) was administered q3 wks as a 30-minute outpatient IV infusion for 2 cycles prior to up to 6 cycles of CHOP. Pts in complete or partial remission (CR, PR) following CHOP were eligible to continue single-agent brentuximab vedotin up to 16 total cycles. Investigator-evaluated response assessments utilize the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). All 13 pts in Arm 1 had sALCL; 10 had ALK- and 3 had ALK+ disease. 9 were male. Median age was 62 years (range, 23-81). The most common (≥6 pts) AEs, regardless of severity, were nausea, peripheral sensory neuropathy, and vomiting. The most common (>1 pt) Grade 3/4 AEs were anemia, fatigue, and peripheral sensory neuropathy; all have improved or resolved. Thus far, no pts had a Grade 5 AE or discontinued due to an AE. All 13 pts were evaluable at Cycle 2 and achieved remission after single-agent brentuximab vedotin (5 CR, 8 PR). Following CHOP, 10/12 evaluable pts maintained remission (7 CR, 3 PR). 2 pts with PR after single-agent brentuximab vedotin experienced PD on CHOP treatment. 3 pts have completed 16 cycles of therapy, all in CR. Sequential therapy with brentuximab vedotin was generally well tolerated and all pts achieved remission after 2 cycles of single-agent therapy. The level of activity observed in newly diagnosed pts with this aggressive lymphoma is promising; a phase 3 randomized study is in development. Disclosure M. Fanale: I have acted as a consultant for and served on Advisory Board for Seattle Genetics, Inc. I have received honoraria and travel expenses from Seattle Genetics, Inc. Seattle Genetics, Inc. has provided research funding to my institution. R. Advani: I have served on scientific advisory boards for Seattle Genetics, Inc., Celgene, and Allos Therapeutics. My institution has received research funding from Seattle Genetics, Inc., Abbott, Genentech, Pharmacyclic, and Allos Therapeutics. N.L. Bartlett: I have acted as a consultant to Seattle Genetics, Inc., and have been reimbursed for travel expenses by Seattle Genetics, Inc. My institution has also received research funding from Seattle Genetics, Inc. A. Davies: I have served on a scientific advisory board for Seattle Genetics, Inc. My institution has also received research funding from Seattle Genetics, Inc. T. Illidge: I have acted as a consultant to Seattle Genetics, Inc. and Millennium/Takeda. I have received honoraria from Millennium/Takeda. My institution has received research funding from Seattle Genetics, Inc. D.A. Kennedy: I am an employee of and have equity ownership in Seattle Genetics, Inc. A.R. Shustov: I have acted as a consultant to Seattle Genetics, Inc. I have received honoraria from Millennium. My institution has received research funding from Seattle Genetics, Inc.