1. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.
- Author
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Kreitman, Robert, Dearden, Claire, Zinzani, Pier, Delgado, Julio, Karlin, Lionel, Robak, Tadeusz, Gladstone, Douglas, le Coutre, Philipp, Dietrich, Sascha, Gotic, Mirjana, Larratt, Loree, Offner, Fritz, Schiller, Gary, Swords, Ronan, Bacon, Larry, Bocchia, Monica, Bouabdallah, Krimo, Breems, Dimitri, Cortelezzi, Agostino, Dinner, Shira, Doubek, Michael, Gjertsen, Bjorn, Gobbi, Marco, Hellmann, Andrzej, Lepretre, Stephane, Maloisel, Frederic, Ravandi, Farhad, Rousselot, Philippe, Rummel, Mathias, Siddiqi, Tanya, Tadmor, Tamar, Troussard, Xavier, Yi, Cecilia, Saglio, Giuseppe, Roboz, Gail, Balic, Kemal, Standifer, Nathan, He, Peng, Marshall, Shannon, Wilson, Wyndham, Pastan, Ira, Yao, Nai-Shun, and Giles, Francis
- Subjects
Adult ,Aged ,Aged ,80 and over ,Antineoplastic Agents ,Bacterial Toxins ,Drug Resistance ,Neoplasm ,Exotoxins ,Female ,Follow-Up Studies ,Humans ,Leukemia ,Hairy Cell ,Male ,Middle Aged ,Neoplasm Recurrence ,Local ,Prognosis ,Remission Induction ,Salvage Therapy ,Survival Rate - 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.
- Published
- 2018