Brentuximab Vedotin in Combination with Chp in Patients (Pts) with Newly-Diagnosed Cd30+ Peripheral T-Cell Lymphomas (Ptcl): 2-Year Follow-Up

Abstract

ABSTRACT Aim: PTCL comprises a subset of aggressive non-Hodgkin lymphomas. Outcomes of frontline treatment (tx) are poor, with complete remission (CR) rates of 39–53% (Reimer 2009; D'Amore 2012) and 5-yr overall survival (OS) rates of 12–49%, depending on subtype (Vose 2008). Brentuximab vedotin (ADCETRIS®; BV) has shown clinical activity in a phase 1 trial of BV in sequence with CHOP or in combination with CHP (CHOP without vincristine; A + CHP) in pts with newly-diagnosed PTCL (Fanale, ASH 2013). Methods: This phase 1, open-label study assessed the safety and efficacy of BV administered sequentially with standard-dose CHOP or in combination with CHP for the frontline tx of PTCL (ClinicalTrials.gov NCT01309789). ALK+ systemic anaplastic large cell lymphoma (sALCL) pts must have had IPI score ≥2. Combination tx included a cohort to determine the recommended dose of BV in A + CHP to be evaluated in an expansion cohort (6 cycles q3wk). Responders could receive single-agent BV (1.8 mg/kg q3wk) for up to 10 additional cycles. Updated progression-free survival (PFS) and OS data from combination tx is presented. Results: The median age of pts was 56 yrs (range, 21–82; n=26). Diagnoses included sALCL (n = 19; 16 ALK-), peripheral T-cell lymphoma-NOS (n = 2), angioimmunoblastic T-cell lymphoma (n = 2), adult T-cell leukemia/lymphoma (n = 2), and enteropathy-associated T-cell lymphoma (n = 1). The maximum tolerated dose of BV in A + CHP was not exceeded at 1.8 mg/kg IV, based on 1 DLT (Grade 3 rash). 23 of 26 pts completed 6 cycles of A + CHP. Treatment-emergent adverse events (≥40%) included peripheral sensory neuropathy, nausea, fatigue, alopecia, diarrhea, and dyspnea. At the end of combination tx, the objective response rate was 100% and CR rate was 88%. After a median observation time of 27.1 months, the 2-yr PFS and OS rates were 54% (95% CI 32, 71) and 80% (95% CI 59, 91), respectively. The estimated median PFS was not reached. No pts went on to receive a consolidative stem cell transplant. Conclusions: A + CHP delivered durable remissions in newly-diagnosed PTCL pts, with a 2-yr PFS rate of 54%. A phase 3 study comparing A + CHP to CHOP in the frontline tx of PTCL is underway (ClinicalTrials.gov NCT01777152). Disclosure: M.A. Fanale: Acted as a consultant for: Seattle Genetics, Inc. Honoraria provided by: Seattle Genetics, Inc. Travel expenses provided by: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; S.M. Horwitz: Consultant: Celgene, Seattle Genetics, Inc., Janssen, Takeda International Pharmaceuticals International Co. Research funding/grants: Takeda International Pharmaceuticals International Co., Kiowa Kirin, Allos, Celgene, Infinity, Seattle Genetics, Inc.; A. Forero-Torres: Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.; N.L. Bartlett: Acted as a consultant for: Seattle Genetics, Inc. Travel expenses provided by: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; R.H. Advani: Research funding/grants: Seattle Genetics, Inc., Genentech, Takeda Pharmaceuticals International Co., Abbott, Allos, Janssen, Pharmacyclics Consultant: Seattle Genetics, Inc., Genentech, Takeda Pharmaceuticals International Co., Celgene; B. Pro: Acted as a consultant for: Seattle Genetics, Inc. Travel expenses provided by:Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; R.W. Chen: Acted as a consultant for:Seattle Genetics, Inc. Travel expenses provided by:Seattle Genetics, Inc. Research funding/grants provided to the authors institution by:Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.; A. Davies: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Takeda Pharmaceuticals International Co.; T. Illidge: Acted as a consultant for: Seattle Genetics, Inc. Takeda Pharmaceuticals International Co. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Takeda Pharmaceuticals International Co.; D. Huebner: Employment: Takeda Pharmaceuticals International Co. Equity ownership (including stock options): Takeda Pharmaceuticals International Co.; D.A. Kennedy: Employment: Seattle Genetics, Inc. Equity ownership (including stock options): Seattle Genetics, Inc.; A.R. Shustov: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.