PMID- 29859255
OWN - NLM
STAT- MEDLINE
DCOM- 20190916
LR  - 20191210
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Linking)
VI  - 24
IP  - 11
DP  - 2018 Nov
TI  - Safety Analysis of Brentuximab Vedotin from the Phase III AETHERA Trial in 
      Hodgkin Lymphoma in the Post-Transplant Consolidation Setting.
PG  - 2354-2359
LID - S1083-8791(18)30298-2 [pii]
LID - 10.1016/j.bbmt.2018.05.026 [doi]
AB  - The phase III AETHERA trial demonstrated the efficacy of brentuximab vedotin (BV) 
      as consolidation therapy in patients with classical Hodgkin lymphoma (HL) at high 
      risk of relapse or progression after autologous hematopoietic stem cell 
      transplantation (auto-HSCT; hazard ratio, .57; P < .001). The objective of this 
      analysis is to provide further detail on the most common and clinically important 
      treatment-emergent adverse events (AEs) in the AETHERA BV arm including their 
      occurrence and management. AEs of clinical importance occurring in patients who 
      participated in AETHERA (BV + best supportive care [BSC], n = 165; placebo + BSC, 
      n = 164) were evaluated for time to onset, manageability through dose 
      modification, and resolution. As previously reported, peripheral neuropathy (PN; 
      67%), infections (60%), and neutropenia (35%) were the most common BV-associated 
      treatment-emergent AEs. Neutropenia was managed with dose delays and granulocyte 
      colony-stimulating factor; no dose reductions or discontinuations were required. 
      Most PN cases (57%) were managed with dose delays and reductions. The median time 
      to PN onset was 13.7 weeks (range, .1 to 47.4). After the end of treatment, PN 
      continued to resolve; symptom resolution was similar to that in the placebo arm 
      at 3 years, demonstrating reversibility. BV had no significant impact on 
      pre-existing PN. Patients with PN-related dose modifications had progression-free 
      survival (PFS) comparable with patients without. Other less common but serious 
      AEs, including pulmonary toxicities, hepatotoxicity, and cardiotoxicity, were 
      rare in both arms and were managed with BV dose modifications or 
      discontinuations. Secondary malignancies were rare and reported in patients with 
      comorbidities or other risk factors. Consolidation therapy with BV for patients 
      with HL at high risk of relapse after auto-HSCT is associated with sustained PFS. 
      The most common AEs in the BV arm were manageable and reversible. Awareness of 
      these AEs and management approaches will enable healthcare providers and patients 
      to plan the safest and most effective treatment plan.
CI  - Copyright (c) 2018 The American Society for Blood and Marrow Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Nademanee, Auayporn
AU  - Nademanee A
AD  - Department of Hematology and Hematopoietic Cell Transplantation, City of Hope 
      National Medical Center, Duarte, California. Electronic address: 
      ANademanee@coh.org.
FAU - Sureda, Anna
AU  - Sureda A
AD  - Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut 
      Catala d'Oncologia, Hospitaet, Barcelona, Spain.
FAU - Stiff, Patrick
AU  - Stiff P
AD  - Cardinal Bernardain Cancer Center, Loyola University Medical Center, Maywood, 
      Illinois.
FAU - Holowiecki, Jerzy
AU  - Holowiecki J
AD  - Department of Bone Marrow Transplantation and Oncohematology, Maria 
      Sklodowska-Curie Institute of Oncology, Gliwice, Poland.
FAU - Abidi, Muneer
AU  - Abidi M
AD  - Bone Marrow Transplant Program, Spectrum Health Cancer Center, Michigan State 
      University, Grand Rapids, Michigan.
FAU - Hunder, Naomi
AU  - Hunder N
AD  - Seattle Genetics, Inc., Bothell, Washington.
FAU - Pecsok, Michael
AU  - Pecsok M
AD  - Seattle Genetics, Inc., Bothell, Washington.
FAU - Uttarwar, Mayur
AU  - Uttarwar M
AD  - Seattle Genetics, Inc., Bothell, Washington.
FAU - Purevjal, Indra
AU  - Purevjal I
AD  - Global Pharmacovigilance Department, Takeda Oncology, Cambridge, Massachusetts.
FAU - Sweetenham, John
AU  - Sweetenham J
AD  - Department of Hematology and Blood and Marrow Transplant, Huntsman Cancer 
      Institute, University of Utah, Salt Lake City, Utah.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180530
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (Immunoconjugates)
RN  - 7XL5ISS668 (Brentuximab Vedotin)
SB  - IM
MH  - Brentuximab Vedotin
MH  - Consolidation Chemotherapy/*methods
MH  - Female
MH  - Hodgkin Disease/*drug therapy/pathology
MH  - Humans
MH  - Immunoconjugates/pharmacology/*therapeutic use
MH  - Male
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Brentuximab vedotin
OT  - Peripheral neuropathy
OT  - Safety
EDAT- 2018/06/03 06:00
MHDA- 2019/09/17 06:00
CRDT- 2018/06/03 06:00
PHST- 2018/01/30 00:00 [received]
PHST- 2018/05/24 00:00 [accepted]
PHST- 2018/06/03 06:00 [pubmed]
PHST- 2019/09/17 06:00 [medline]
PHST- 2018/06/03 06:00 [entrez]
AID - S1083-8791(18)30298-2 [pii]
AID - 10.1016/j.bbmt.2018.05.026 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2018 Nov;24(11):2354-2359. doi: 
      10.1016/j.bbmt.2018.05.026. Epub 2018 May 30.