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Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 20.

Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.

Author information

1
National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
2
The Royal Marsden NHS Foundation Trust, London, UK.
3
Institute of Hematology, Seràgnoli University of Bologna, Bologna, Italy.
4
Hospital Clinic, Barcelona, Spain.
5
Centre Hospitalier Lyon Sud, Pierre-bénite, France.
6
Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.
7
Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.
8
Charité Universitätsmedizin, Berlin, Germany.
9
Universitätsklinikum Heidelberg, Heidelberg, Baden-Württemberg, Germany.
10
Clinical Center of Serbia, Belgrade, Serbia.
11
University of Alberta, Edmonton, Alberta, Canada.
12
Ghent University Hospital, Ghent, Belgium.
13
David Geffen School of Medicine, UCLA, Los Angeles, CA, USA.
14
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
15
St. James's Hospital, Dublin, Ireland.
16
Azienda Ospedaliera Universitaria, University of Siena, Siena, Italy.
17
Service d'hématologie, CHU Bordeaux, F-33000, Bordeaux, France.
18
Ziekenhuis Netwerk Antwerpe, Antwerp, Belgium.
19
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
20
Northwestern Medicine Feinberg School of Medicine, Chicago, IL, USA.
21
Masaryk University, Brno, Czech Republic.
22
Helse Bergen HF Haukeland University Hospital, Bergen, Norway.
23
Clinic of Hematology, Ospedale Policlinico San Martino, Genova, Italy.
24
Department of Hematology and Transplantation, Medical University of Gdańsk, Gdańsk, Poland.
25
Inserm U1245 and Department of Hematology, Centre Henri Becquerel and Normandie Univ UNIROUEN, Rouen, France.
26
SOL, Clinique Sainte-Anne, Strasbourg, France.
27
MD Anderson Cancer Center, Houston, TX, USA.
28
Centre Hospitalier de Versailles, INSERM U1173, Le Chesnay, France.
29
Université Versailles Saint-Quentin-en-Yvelines, Paris Saclay, France.
30
Justus-Liebig University, Giessen, Germany.
31
City of Hope National Medical Center, Duarte, CA, USA.
32
Bnai Zion Medical Center, Haifa, Israel.
33
L'hôpital Côte de Nacre, Caen Cedex 9, Caen, France.
34
University of New Mexico, Albuquerque, NM, USA.
35
University of Turin, Turin, Italy.
36
Weill Cornell Medicine, The New York Presbyterian Hospital, New York, NY, USA.
37
MedImmune, South San Francisco, CA, USA.
38
MedImmune, Gaithersburg, MD, USA.
39
Developmental Therapeutics Consortium, Chicago, IL, USA. frankgiles@aol.com.

Abstract

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 µg/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.

PMID:
30030507
PMCID:
PMC6087717
DOI:
10.1038/s41375-018-0210-1
[Indexed for MEDLINE]
Free PMC Article

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