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.

Azienda Ospedaliera Universitaria University of Siena Siena Italy

Bnai Zion Medical Center Haifa Israel

Centre Hospitalier de Versailles INSERM U1173 Le Chesnay France

Centre Hospitalier Lyon Sud Pierre bénite France

Charité Universitätsmedizin Berlin Germany

City of Hope National Medical Center Duarte CA USA

Clinic of Hematology Ospedale Policlinico San Martino Genova Italy

Clinical Center of Serbia Belgrade Serbia

David Geffen School of Medicine UCLA Los Angeles CA USA

Department of Hematology and Transplantation Medical University of Gdańsk Gdańsk Poland

Developmental Therapeutics Consortium Chicago IL USA

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico University of Milan Milan Italy

Ghent University Hospital Ghent Belgium

Helse Bergen HF Haukeland University Hospital Bergen Norway

Hospital Clinic Barcelona Spain

Inserm U1245 and Department of Hematology Centre Henri Becquerel and Normandie Univ UNIROUEN Rouen France

Institute of Hematology Seràgnoli University of Bologna Bologna Italy

Johns Hopkins Kimmel Cancer Center Baltimore MD USA

Justus Liebig University Giessen Germany

L'hôpital Côte de Nacre Caen Cedex 9 Caen France

Masaryk University Brno Czech Republic

MD Anderson Cancer Center Houston TX USA

Medical University of Lodz Copernicus Memorial Hospital Lodz Poland

MedImmune Gaithersburg MD USA

MedImmune South San Francisco CA USA

National Cancer Institute National Institutes of Health Bethesda MD USA

Northwestern Medicine Feinberg School of Medicine Chicago IL USA

Service d'hématologie CHU Bordeaux F 33000 Bordeaux France

SOL Clinique Sainte Anne Strasbourg France

St James's Hospital Dublin Ireland

Sylvester Comprehensive Cancer Center University of Miami Miami FL USA

The Royal Marsden NHS Foundation Trust London UK

Universitätsklinikum Heidelberg Heidelberg Baden Württemberg Germany

Université Versailles Saint Quentin en Yvelines Paris Saclay France

University of Alberta Edmonton Alberta Canada

University of New Mexico Albuquerque NM USA

University of Turin Turin Italy

Weill Cornell Medicine The New York Presbyterian Hospital New York NY USA

Ziekenhuis Netwerk Antwerpe Antwerp Belgium

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Allogeneic hematopoietic cell transplant for hairy cell leukemia: EBMT experience

Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas