Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

Robert Kreitman (1) , Claire Dearden (2) , Pier Luigi Zinzani (3) , Julio Delgado (4) , Lionel Karlin (5) , Tadeusz Robak (6) , Douglas Gladstone (7) , Philipp Le Coutre (8) , Sascha Dietrich (9) , Mirjana Gotic (10) , Loree Larratt (11) , Fritz Offner (12) , Gary Schiller (13) , Ronan Swords (14) , Larry Bacon (15) , Monica Bocchia (16) , Krimo Bouabdallah (17) , Dimitri Breems (18) , Agostino Cortelezzi (19) , Shira Dinner (20) , Michael Doubek (21) , Bjørn Tore Gjertsen (22) , Marco Gobbi (23) , Andrzej Hellmann (24) , Stéphane Leprêtre (25, 26) , Frédéric Maloisel (27) , Farhad Ravandi (28) , Philipp Rousselot (29) , Mathias Rummel (30) , Tanya Siddiqi (31) , Tamar Tadmor (32) , Xavier Troussard (33) , Cecilia Arana Yi (34) , Giuseppe Saglio (35) , Gail Roboz (36) , Kemal Balic (37) , Nathan Standifer (37) , Peng He (37) , Shannon Marshall (37) , Wyndham Wilson (38) , Ira Pastan (38) , Nai-Shun Yao (37) , Francis Giles (20)

1 NCI-NIH - National Cancer Institute [Bethesda]
2 Royal Marsden NHS Foundation Trust
3 University of Bologna/Università di Bologna
4 CRESIB - Barcelona Centre for International Health Research, Hospital Clinic
5 Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL]
6 MUL - Medical University of Łódź
7 JHU - Johns Hopkins University
8 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
9 Universität Heidelberg [Heidelberg]
10 KCS - Clinical Center of Serbia
11 University of Alberta
12 UGENT - Universiteit Gent = Ghent University
13 David Geffen School of Medicine [Los Angeles]
14 University of Miami [Coral Gables]
15 St James's University Hospital
16 UNISI - Università degli Studi di Siena = University of Siena
17 CHU Bordeaux [Bordeaux]
18 ZNA - Ziekenhuis Netwerk Antwerpen
19 UNIMI - Università degli Studi di Milano = University of Milan
20 Northwestern University Feinberg School of Medicine
21 SCI / MUNI - Faculty of Science [Brno]
22 Haukeland University Hospital
23 Ospedale Policlinico San Martino [Genoa]
24 Medical University of Gdańsk
25 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
26 CLCC Henri Becquerel - Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen
27 Clinique Sainte Anne [Strasbourg]
28 MD Anderson Cancer Center [Houston]
29 2I - Infection et inflammation
30 JLU - Justus-Liebig-Universität Gießen = Justus Liebig University
31 City of Hope National Medical Center
32 Bnai Zion Medical Center [Israël]
33 Hôpital Côte de Nacre [CHU Caen]
34 The University of New Mexico [Albuquerque]
35 UNITO - Università degli studi di Torino = University of Turin
36 New York Presbyterian Hospital
37 MedImmune
38 NIH - National Institutes of Health [Bethesda]

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.

Domains: Life Sciences [q-bio]; Pharmaceutical sciences; Pharmacology; Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Human health and pathology; Hematology

Robert Kreitman, Claire Dearden, Pier Luigi Zinzani, Julio Delgado, Lionel Karlin, et al.. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia, 2018, 32 (8), pp.1768-1777. ⟨10.1038/s41375-018-0210-1⟩. ⟨hal-02194148⟩