Journal articles

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

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 [Belgium]

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 [Milano]

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]

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Pharmaceutical sciences / Pharmacology

Life Sciences [q-bio] / Cancer

Life Sciences [q-bio] / Human health and pathology / Hematology

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Submitted on : Thursday, July 25, 2019 - 11:38:53 AM
Last modification on : Friday, March 11, 2022 - 6:14:02 PM