PMID- 30030507
OWN - NLM
STAT- MEDLINE
DCOM- 20190521
LR  - 20190521
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 32
IP  - 8
DP  - 2018 Aug
TI  - Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.
PG  - 1768-1777
LID - 10.1038/s41375-018-0210-1 [doi]
AB  - This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a 
      recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B 
      cell malignancy with high CD22 expression. The study enrolled patients with 
      relapsed/refractory HCL who had >/=2 prior systemic therapies, including >/=1 purine 
      nucleoside analog. Patients received moxetumomab pasudotox 40 microg/kg intravenously 
      on days 1, 3, and 5 every 28 days for </=6 cycles. Blinded independent central 
      review determined disease response and minimal residual disease (MRD) status. 
      Among 80 patients (79% males; median age, 60.0 years), durable complete response 
      (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial 
      response) was 75%; 64 patients (80%) achieved hematologic remission. Among 
      complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. 
      The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), 
      fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic 
      uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and 
      generally manageable with supportive care and treatment discontinuation (6 
      patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of 
      independently assessed durable response and MRD eradication in heavily pretreated 
      patients with HCL, with acceptable tolerability.
FAU - Kreitman, Robert J
AU  - Kreitman RJ
AD  - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Dearden, Claire
AU  - Dearden C
AD  - The Royal Marsden NHS Foundation Trust, London, UK.
FAU - Zinzani, Pier Luigi
AU  - Zinzani PL
AD  - Institute of Hematology, Seragnoli University of Bologna, Bologna, Italy.
FAU - Delgado, Julio
AU  - Delgado J
AD  - Hospital Clinic, Barcelona, Spain.
FAU - Karlin, Lionel
AU  - Karlin L
AD  - Centre Hospitalier Lyon Sud, Pierre-benite, France.
FAU - Robak, Tadeusz
AU  - Robak T
AD  - Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
FAU - Gladstone, Douglas E
AU  - Gladstone DE
AUID- ORCID: 0000-0001-8484-2990
AD  - Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.
FAU - le Coutre, Philipp
AU  - le Coutre P
AD  - Charite Universitatsmedizin, Berlin, Germany.
FAU - Dietrich, Sascha
AU  - Dietrich S
AD  - Universitatsklinikum Heidelberg, Heidelberg, Baden-Wurttemberg, Germany.
FAU - Gotic, Mirjana
AU  - Gotic M
AUID- ORCID: 0000-0002-8590-0328
AD  - Clinical Center of Serbia, Belgrade, Serbia.
FAU - Larratt, Loree
AU  - Larratt L
AD  - University of Alberta, Edmonton, Alberta, Canada.
FAU - Offner, Fritz
AU  - Offner F
AD  - Ghent University Hospital, Ghent, Belgium.
FAU - Schiller, Gary
AU  - Schiller G
AD  - David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
FAU - Swords, Ronan
AU  - Swords R
AD  - Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
FAU - Bacon, Larry
AU  - Bacon L
AD  - St. James's Hospital, Dublin, Ireland.
FAU - Bocchia, Monica
AU  - Bocchia M
AD  - Azienda Ospedaliera Universitaria, University of Siena, Siena, Italy.
FAU - Bouabdallah, Krimo
AU  - Bouabdallah K
AD  - Service d'hematologie, CHU Bordeaux, F-33000, Bordeaux, France.
FAU - Breems, Dimitri A
AU  - Breems DA
AD  - Ziekenhuis Netwerk Antwerpe, Antwerp, Belgium.
FAU - Cortelezzi, Agostino
AU  - Cortelezzi A
AD  - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, 
      Milan, Italy.
FAU - Dinner, Shira
AU  - Dinner S
AD  - Northwestern Medicine Feinberg School of Medicine, Chicago, IL, USA.
FAU - Doubek, Michael
AU  - Doubek M
AD  - Masaryk University, Brno, Czech Republic.
FAU - Gjertsen, Bjorn Tore
AU  - Gjertsen BT
AUID- ORCID: 0000-0001-9358-9704
AD  - Helse Bergen HF Haukeland University Hospital, Bergen, Norway.
FAU - Gobbi, Marco
AU  - Gobbi M
AD  - Clinic of Hematology, Ospedale Policlinico San Martino, Genova, Italy.
FAU - Hellmann, Andrzej
AU  - Hellmann A
AD  - Department of Hematology and Transplantation, Medical University of Gdansk, 
      Gdansk, Poland.
FAU - Lepretre, Stephane
AU  - Lepretre S
AD  - Inserm U1245 and Department of Hematology, Centre Henri Becquerel and Normandie 
      Univ UNIROUEN, Rouen, France.
FAU - Maloisel, Frederic
AU  - Maloisel F
AD  - SOL, Clinique Sainte-Anne, Strasbourg, France.
FAU - Ravandi, Farhad
AU  - Ravandi F
AD  - MD Anderson Cancer Center, Houston, TX, USA.
FAU - Rousselot, Philippe
AU  - Rousselot P
AD  - Centre Hospitalier de Versailles, INSERM U1173, Le Chesnay, France.
AD  - Universite Versailles Saint-Quentin-en-Yvelines, Paris Saclay, France.
FAU - Rummel, Mathias
AU  - Rummel M
AD  - Justus-Liebig University, Giessen, Germany.
FAU - Siddiqi, Tanya
AU  - Siddiqi T
AD  - City of Hope National Medical Center, Duarte, CA, USA.
FAU - Tadmor, Tamar
AU  - Tadmor T
AD  - Bnai Zion Medical Center, Haifa, Israel.
FAU - Troussard, Xavier
AU  - Troussard X
AD  - L'hopital Cote de Nacre, Caen Cedex 9, Caen, France.
FAU - Yi, Cecilia Arana
AU  - Yi CA
AD  - University of New Mexico, Albuquerque, NM, USA.
FAU - Saglio, Giuseppe
AU  - Saglio G
AD  - University of Turin, Turin, Italy.
FAU - Roboz, Gail J
AU  - Roboz GJ
AD  - Weill Cornell Medicine, The New York Presbyterian Hospital, New York, NY, USA.
FAU - Balic, Kemal
AU  - Balic K
AD  - MedImmune, South San Francisco, CA, USA.
FAU - Standifer, Nathan
AU  - Standifer N
AD  - MedImmune, South San Francisco, CA, USA.
FAU - He, Peng
AU  - He P
AD  - MedImmune, Gaithersburg, MD, USA.
FAU - Marshall, Shannon
AU  - Marshall S
AD  - MedImmune, Gaithersburg, MD, USA.
FAU - Wilson, Wyndham
AU  - Wilson W
AD  - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Pastan, Ira
AU  - Pastan I
AD  - National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Yao, Nai-Shun
AU  - Yao NS
AD  - MedImmune, Gaithersburg, MD, USA.
FAU - Giles, Francis
AU  - Giles F
AD  - Developmental Therapeutics Consortium, Chicago, IL, USA. frankgiles@aol.com.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180720
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Exotoxins)
RN  - 2NDX4B6N8F (immunotoxin HA22)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Bacterial Toxins/*therapeutic use
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Exotoxins/*therapeutic use
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Leukemia, Hairy Cell/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Prognosis
MH  - Remission Induction
MH  - *Salvage Therapy
MH  - Survival Rate
PMC - PMC6087717
COIS- This study was sponsored by MedImmune. RJK received a research grant from 
      MedImmune and is co-inventor of moxetumomab pasudotox, with the NIH holding the 
      patent. CD has received personal fees from Gilead, Infinity, 
      Janssen/Pharacyclics, MedImmune, Roche, and Sanofi Aventis, and has received 
      clinical trial support from MedImmune. PLZ has served as an advisor for 
      Bristol-Myers Squibb, Celgene, Gilead, Janssen, Merck, Roche, Servier, and 
      Takeda. JD served on a data monitoring board for MedImmune, has received research 
      grants from Janssen and Roche, and has received personal fees from Abbvie, 
      Gilead, Janssen, and Roche. LK, DEG, M Gotic, LL, FO, RS, GS, SD, LB, CAY, AH, 
      KB, MB, MG, AC, MD, SD, SL, MR, PR, TT, GS, GJR, XT, and WW have no conflicts to 
      report. TR has received research grants from AstraZeneca. PLC has served as a 
      speaker for Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. DAB has received 
      personal fees from Amgen, Novartis, and Teva, and his institution has received 
      reimbursement for clinical trials from Ablynx, Amgen, Astellas, Astex, Cyclacel, 
      Genzyme, Janssen, MedImmune, Merus, Menarini, Novella Clinical, Pfizer, and 
      Seattle Genetics. BTG has received personal fees from BerGenBio AS, Novartis AS, 
      Pfizer, and Seattle Genetics, received non-financial support from Merck Sharpe & 
      Dohme and Roche, and owns shares in Alden Cancer Therapeutics 2 AS and Kinn 
      Therapeutics AS. FM has received research grants from Amgen and Sandoz, received 
      travel accommodations from Octapharma and Roche, and served on advisory boards 
      for Pfizer, Roche, and Sandoz. FR has received research grants from MedImmune. TS 
      has served on speakers' bureaus for Pharmacyclics and Seattle Genetics, and on a 
      steering committee for Juno. KB, NS, PH, SM, and NSY are employees of MedImmune 
      and may own stock/options in AstraZeneca. IP is co-inventor of moxetumomab 
      pasudotox, with the NIH holding the patent. FG has received a research grant from 
      MedImmune.
EDAT- 2018/07/22 06:00
MHDA- 2019/05/22 06:00
PMCR- 2018/07/20
CRDT- 2018/07/22 06:00
PHST- 2018/06/06 00:00 [received]
PHST- 2018/06/08 00:00 [accepted]
PHST- 2018/07/22 06:00 [pubmed]
PHST- 2019/05/22 06:00 [medline]
PHST- 2018/07/22 06:00 [entrez]
PHST- 2018/07/20 00:00 [pmc-release]
AID - 10.1038/s41375-018-0210-1 [pii]
AID - 210 [pii]
AID - 10.1038/s41375-018-0210-1 [doi]
PST - ppublish
SO  - Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 
      20.