944O - Brentuximab vedotin in combination with CHP in patients (Pts) with newly-diagnosed CD30+ peripheral T-cell lymphomas (PTCL): 2-year follow-up

Date 29 September 2014
Event ESMO 2014
Session Haematological malignancies
Topics Anticancer agents
Lymphomas
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Therapy
Biological Therapy
Presenter Michelle Fanale
Citation Annals of Oncology (2014) 25 (suppl_4): iv327-iv339. 10.1093/annonc/mdu339
Authors M.A. Fanale1, S.M. Horwitz2, A. Forero-Torres3, N.L. Bartlett4, R.H. Advani5, B. Pro6, R.W. Chen7, A. Davies8, T. Illidge9, D. Huebner10, D.A. Kennedy11, A.R. Shustov12
  • 1Medical Oncology Hematology, University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 3Medical Oncology Hematology, University of Alabama at Birmingham, Birmingham/US
  • 4Medical Oncology Hematology, Washington University School of Medicine, St. Louis/US
  • 5Medical Oncology Hematology, Stanford University Medical Center, Palo Alto/US
  • 6Medical Oncology Hematology, Fox Chase Cancer Center, Philadelphia/US
  • 7Medical Oncology Hematology, City of Hope National Medical Center, Duarte/US
  • 8Medical Oncology Hematology, Southampton University Hospitals Trust, Southampton/GB
  • 9Medical Oncology Hematology, Christie Hospital NHS, Manchester/GB
  • 10Clinical Development, Takeda Pharmaceuticals International Co., Cambridge/US
  • 11Clinical Affairs, Seattle Genetics, Inc., Bothell/US
  • 12Medical Oncology Hematology, University of Washington Medical Center, Seattle/US

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.