PMID- 26858336
OWN - NLM
STAT- MEDLINE
DCOM- 20160809
LR  - 20240327
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 34
IP  - 10
DP  - 2016 Apr 1
TI  - First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain 
      Amyloidosis and Persistent Organ Dysfunction.
PG  - 1097-103
LID - 10.1200/JCO.2015.63.6530 [doi]
AB  - PURPOSE: Light chain (AL) amyloidosis is caused by the accumulation of misfolded 
      proteins, which induces the dysfunction of vital organs. NEOD001 is a monoclonal 
      antibody targeting these misfolded proteins. We report interim data from a phase 
      I/II dose-escalation/expansion study of NEOD001 in patients with AL amyloidosis 
      and persistent organ dysfunction (NCT01707264). PATIENTS AND METHODS: Patients 
      who had completed at least one previous anti-plasma cell-directed therapy, had 
      partial hematologic response or better, and had persistent organ dysfunction 
      received NEOD001 intravenously every 28 days. Dose levels of 0.5, 1, 2, 4, 8, 16, 
      and 24 mg/kg were evaluated (3 + 3 study design). Primary objectives were to 
      determine the maximum tolerated dose and the recommended dose for future studies 
      and to evaluate safety/tolerability. Secondary and exploratory objectives 
      included pharmacokinetics, immunogenicity, and organ responses on the basis of 
      published consensus criteria. RESULTS: Twenty-seven patients were enrolled in 
      seven cohorts (dose-escalation component). No drug-related serious adverse events 
      (AEs), discontinuations because of drug-related AEs, dose-limiting toxicities, or 
      antidrug antibodies were reported. The most frequent AEs were fatigue, upper 
      respiratory tract infection, cough, and dyspnea. Recommended dosing was 24 mg/kg. 
      Pharmacokinetics support intravenous dosing every 28 days. Of 14 
      cardiac-evaluable patients, eight (57%) met the criteria for cardiac response and 
      six (43%) had stable disease. Of 15 renal-evaluable patients, nine (60%) met the 
      criteria for renal response and six (40%) had stable disease. CONCLUSION: Monthly 
      infusions of NEOD001 were safe and well tolerated. Recommended future dosing was 
      24 mg/kg. Organ response rates compared favorably with those reported previously 
      for chemotherapy. A phase II expansion is ongoing. A global phase III study 
      (NCT02312206) has been initiated. Antibody therapy targeting misfolded proteins 
      is a potential new therapy for the management of AL amyloidosis.
CI  - (c) 2016 by American Society of Clinical Oncology.
FAU - Gertz, Morie A
AU  - Gertz MA
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA 
      gertz.morie@mayo.edu.
FAU - Landau, Heather
AU  - Landau H
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Comenzo, Raymond L
AU  - Comenzo RL
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Seldin, David
AU  - Seldin D
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Weiss, Brendan
AU  - Weiss B
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Zonder, Jeffrey
AU  - Zonder J
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Merlini, Giampaolo
AU  - Merlini G
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Schonland, Stefan
AU  - Schonland S
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Walling, Jackie
AU  - Walling J
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Kinney, Gene G
AU  - Kinney GG
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Koller, Martin
AU  - Koller M
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Schenk, Dale B
AU  - Schenk DB
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Guthrie, Spencer D
AU  - Guthrie SD
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
FAU - Liedtke, Michaela
AU  - Liedtke M
AD  - Morie A. Gertz, Mayo Clinic, Rochester, MN; Heather Landau, Memorial Sloan 
      Kettering Cancer Center, New York, NY; Raymond L. Comenzo, Tufts Medical Center; 
      David Seldin, Boston University, Boston, MA; Brendan Weiss, University of 
      Pennsylvania, Philadelphia, PA; Jeffrey Zonder, Karmanos Cancer Institute, 
      Detroit, MI; Giampaolo Merlini, Fondazione Instituto Di Ricovero e Cura a 
      Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, 
      Italy; Stefan Schonland, University of Heidelberg, Heidelberg, Germany; Jackie 
      Walling, JW Consulting, Hillsborough; Gene G. Kinney, Martin Koller, Dale B. 
      Schenk, and Spencer D. Guthrie, Prothena Biosciences, Inc., South San Francisco; 
      and Michaela Liedtke, Stanford University School of Medicine, Stanford, CA.
LA  - eng
SI  - ClinicalTrials.gov/NCT01707264
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160208
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Immunoglobulin Light Chains)
RN  - VXQ2SK8I3P (birtamimab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amyloidosis/complications/*drug therapy/ethnology/*immunology
MH  - Antibodies, Monoclonal, Humanized/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Cough/chemically induced
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Dyspnea/chemically induced
MH  - Fatigue/chemically induced
MH  - Female
MH  - Heart/drug effects/physiopathology
MH  - Humans
MH  - *Immunoglobulin Light Chains/immunology
MH  - Kidney/drug effects/physiopathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Multiple Organ Failure/*etiology/physiopathology/*prevention & control
MH  - Plasma Cells/*drug effects/immunology
MH  - Respiratory Tract Infections/chemically induced
MH  - Treatment Outcome
PMC - PMC5470113
COIS- Authors' disclosures of potential conflicts of interest are found in the article 
      online at www.jco.org. Author contributions are found at the end of this article.
EDAT- 2016/02/10 06:00
MHDA- 2016/08/10 06:00
PMCR- 2016/02/08
CRDT- 2016/02/10 06:00
PHST- 2016/02/10 06:00 [entrez]
PHST- 2016/02/10 06:00 [pubmed]
PHST- 2016/08/10 06:00 [medline]
PHST- 2016/02/08 00:00 [pmc-release]
AID - JCO.2015.63.6530 [pii]
AID - 636530 [pii]
AID - 10.1200/JCO.2015.63.6530 [doi]
PST - ppublish
SO  - J Clin Oncol. 2016 Apr 1;34(10):1097-103. doi: 10.1200/JCO.2015.63.6530. Epub 
      2016 Feb 8.