Journal Article

Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

Swords, Ronan, Offner, Fritz, Gobbi, Marco, Cecilia Arana Yi, Karlin, Lionel, Lepretre, Stephane, Robak, Tadeusz, Marshall, Shannon, Cortelezzi, Agostino, Dinner, Shira, Doubek, Michael, Rousselot, Philippe, Balic, Kemal, Zinzani, Pier Luigi, Gjertsen, Bjorn Tore, Giles, Francis, Yao, Nai-Shun, Gladstone, Douglas E, Saglio, Giuseppe, Rummel, Mathias, Siddiqi, Tanya, Roboz, Gail J, Bocchia, Monica, Dearden, Claire, Wilson, Wyndham, Ravandi, Farhad, Troussard, Xavier, Philipp le Coutre, Schiller, Gary, Maloisel, Frederic, Larratt, Loree, Tadmor, Tamar, Standifer, Nathan, Hellmann, Andrzej, Gotic, Mirjana, He, Peng, Dietrich, Sascha, Kreitman, Robert J, Delgado, Julio, Bouabdallah, Krimo, Pastan, Ira, Breems, Dimitri A, Bacon, Larry

2018

Overview

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.

• Publisher: Nature Publishing Group
• Subject: CD22 antigen / Edema / Eradication / Fatigue / Hairy cell leukemia / Headache / Hemolytic uremic syndrome / Immunohistochemistry / Immunotherapy / Leukemia / Lymphocytes B / Males / Malignancy / Minimal residual disease / Monoclonal antibodies / Nausea / Nucleoside analogs / Patients / Remission / Targeted cancer therapy