Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

作者：Kreitman, Robert J.; Dearden, Claire; Zinzani, Pier Luigi; Delgado, Julio; Karlin, Lionel; Robak, Tadeusz; Gladstone, Douglas E.; le Coutre, Philipp; Dietrich, Sascha; Gotic, Mirjana; Larratt, Loree; Offner, Fritz; Schiller, Gary; Swords, Ronan; Bacon, Larry; Bocchia, Monica; Bouabdallah, Krimo; Breems, Dimitri A.; Cortelezzi, Agostino; Dinner, Shira; Doubek, Michael; Gjertsen, Bjorn Tore; Gobbi, Marco; Hellmann, Andrzej; Lepretre, Stephane; Maloisel, Frederic; Ravandi, Farhad

来源：Leukemia, 2018, 32(8): 1768-1777.

DOI：10.1038/s41375-018-0210-1

• MINIMAL RESIDUAL DISEASE
• TERM-FOLLOW-UP
• CLADRIBINE
• RITUXIMAB
• IMMUNOHISTOCHEMISTRY
• ERADICATION
• DIAGNOSIS
• EFFICACY
• PATTERNS
• ANTIBODY

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 mu g/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.

• 出版日期2018-8