T031 (0110) FIVE-YEAR PROGRESSION-FREE SURVIVAL OUTCOMES FROM A PIVOTAL PHASE 3 STUDY OF CONSOLIDATIVE BRENTUXIMAB VEDOTIN AFTER AUTOLOGOUS STEM CELL TRANSPLANT IN PATIENTS WITH HODGKIN LYMPHOMA AT RISK OF RELAPSE OR PROGRESSION (AETHERA)

doi: 10.1097/01.HS9.0000547954.06005.08
Relapsed/Refractory HL
Free

Craig H. Moskowitz1, Jan Walewski2, Auayporn Nademanee3, Tamas Masszi4, Edward Agura5, Jerzy Holowiecki6, Muneer H. Abidi7, Andy I. Chen8, Patrick Stiff9, Simonetta Viviani10, Veronika Bachanova11, Anna Sureda12, Teresa McClendon13, Connie Lee14, Julie Lisano13, John Sweetenham15

1 Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL, USA, 2 Department of Lymphoid Malignancies, Maria Sklodowska-Curie Memorial Institute and Oncology Centre, Warsaw, Poland, 3 Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA, 4 3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary, 5 Blood and Marrow Transplantation, Baylor University Medical Center, Dallas, TX, USA, 6 Department of Bone Marrow Transplantation & Oncohematology, Maria Sklodowska-Curie Institute of Oncology, Gliwice, Poland, 7 Bone Marrow Transplant Program, Spectrum Health Cancer Center, Michigan State University, Grand Rapids, MI, USA, 8 Oregon Health & Science University, Portland, Oregon, USA, 9 Cardinal Bernardain Cancer Center, Loyola University Medical Center, Maywood, IL, USA, 10 Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, 11 University of Minnesota, Minneapolis, MN, USA, 12 Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d‘Oncologia, Hospital Duran i Reynals, Barcelona, Spain, 13 Seattle Genetics, Inc, Bothell, WA, USA, 14 Takeda Oncology, Cambridge, MA, USA, 15 Department of Hematology and Blood and Marrow Transplant, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for patients with classical Hodgkin lymphoma (cHL) at high risk of relapse/progression following autologous hematopoietic stem cell transplant (auto-HSCT).1 Results showed that BV significantly improved progression-free survival (PFS) vs placebo plus best supportive care (placebo) alone (hazard ratio [HR], 0.57; P = .001). Here we present updated data at 5 years of follow-up.

Patients with HL must have received auto-HSCT before randomization and have been at high risk of relapse after auto-HSCT based on having either relapsed/progressive HL occurring < 12 months from the end of frontline therapy; a history of refractory HL; or extranodal involvement before auto-HSCT relapse. A total of 329 patients were randomized to receive BV 1.8 mg/kg or placebo Q3W for up to 16 cycles starting 30–45 days after auto-HSCT.

At 5 years, BV continued to provide a PFS benefit; 5-year PFS was 59% (95% CI, 51%–66%) in the BV arm vs 41% (95% CI, 33%–49%) in the placebo arm (HR, 0.521 [95% CI, 0.379–0.717]) (Figure). Patients with ≥ 2 or ≥ 3 risk factors in the BV arm experienced a significantly higher PFS benefit than patients in the placebo arm (HR, 0.424 [95% CI, 0.302–0.596]; HR, 0.390 [95% CI, 0.255–0.596], respectively). An analysis of subsequent therapies was performed to measure ongoing disease control before a planned overall survival analysis in 2020. At 5 years, 36% and 46% of patients in the BV and placebo arms, respectively, had received ≥ 2 subsequent HL therapies or had died (HR, 0.656 [95% CI, 0.467–0.922]); 40 and 37 deaths occurred in each arm, respectively. The majority (87%) of patients in the placebo arm received BV as subsequent therapy, and subsequent HSCT was less frequent in the BV arm (12%) than in the placebo arm (21%). Peripheral neuropathy (PN), the most common adverse event in the BV arm, continued to improve and/or resolve: at 5 years, 90% of patients reported their PN as resolved or improved, including 73% with complete resolution.

Consolidation with BV in patients with cHL at high risk of relapse/progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. These data demonstrate a reduction in the need for subsequent therapy in patients who received BV as consolidation after first auto-HSCT, even when most patients in the placebo arm received subsequent BV at relapse.

1. Moskowitz CH, et al. Lancet 2015;385:1853–1862.

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Copyright © 2018 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.