Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia

Robert J. Kreitman, Claire Dearden, Pier Luigi Zinzani, Julio Delgado, Lionel Karlin, Tadeusz Robak, Douglas Gladstone, Philipp le Coutre, Sascha Dietrich, Mirjana Gotic, Loree Larratt, Fritz Offner, Gary Schiller, Ronan Swords, Larry Bacon, Monica Bocchia, Krimo Bouabdallah, Dimitri A. Breems, Agostino Cortelezzi, Shira Dinner & 23 others Michael Doubek, Bjorn Tore Gjertsen, Marco Gobbi, Andrzej Hellmann, Stephane Lepretre, Frederic Maloisel, Farhad Ravandi, Philippe Rousselot, Mathias Rummel, Tanya Siddiqi, Tamar Tadmor, Xavier Troussard, Cecilia Arana Yi, Giuseppe Saglio, Gail J. Roboz, Kemal Balic, Nathan Standifer, Peng He, Shannon Marshall, Wyndham Wilson, Ira Pastan, Nai Shun Yao, Francis Giles

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1768-1777
Number of pages10
JournalLeukemia
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2018

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Hairy Cell Leukemia
Residual Neoplasm
Capillary Leak Syndrome
Disease Eradication
Purine Nucleosides
Immunotoxins
Hemolytic-Uremic Syndrome
Therapeutics
Nausea
Fatigue
Headache
immunotoxin HA22
Edema
B-Lymphocytes
Immunohistochemistry
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Kreitman, R. J., Dearden, C., Zinzani, P. L., Delgado, J., Karlin, L., Robak, T., ... Giles, F. (2018). Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia, 32(8), 1768-1777. https://doi.org/10.1038/s41375-018-0210-1

Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. / Kreitman, Robert J.; Dearden, Claire; Zinzani, Pier Luigi; 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 A.; Cortelezzi, Agostino; Dinner, Shira; Doubek, Michael; Gjertsen, Bjorn Tore; Gobbi, Marco; Hellmann, Andrzej; Lepretre, Stephane; Maloisel, Frederic; Ravandi, Farhad; Rousselot, Philippe; Rummel, Mathias; Siddiqi, Tanya; Tadmor, Tamar; Troussard, Xavier; Yi, Cecilia Arana; Saglio, Giuseppe; Roboz, Gail J.; Balic, Kemal; Standifer, Nathan; He, Peng; Marshall, Shannon; Wilson, Wyndham; Pastan, Ira; Yao, Nai Shun; Giles, Francis.

In: Leukemia, Vol. 32, No. 8, 01.08.2018, p. 1768-1777.

Research output: Contribution to journalArticle

Kreitman, RJ, Dearden, C, Zinzani, PL, Delgado, J, Karlin, L, Robak, T, Gladstone, D, le Coutre, P, Dietrich, S, Gotic, M, Larratt, L, Offner, F, Schiller, G, Swords, R, Bacon, L, Bocchia, M, Bouabdallah, K, Breems, DA, Cortelezzi, A, Dinner, S, Doubek, M, Gjertsen, BT, Gobbi, M, Hellmann, A, Lepretre, S, Maloisel, F, Ravandi, F, Rousselot, P, Rummel, M, Siddiqi, T, Tadmor, T, Troussard, X, Yi, CA, Saglio, G, Roboz, GJ, Balic, K, Standifer, N, He, P, Marshall, S, Wilson, W, Pastan, I, Yao, NS & Giles, F 2018, 'Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia', Leukemia, vol. 32, no. 8, pp. 1768-1777. https://doi.org/10.1038/s41375-018-0210-1
Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug 1;32(8):1768-1777. https://doi.org/10.1038/s41375-018-0210-1
Kreitman, Robert J. ; Dearden, Claire ; Zinzani, Pier Luigi ; 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 A. ; Cortelezzi, Agostino ; Dinner, Shira ; Doubek, Michael ; Gjertsen, Bjorn Tore ; Gobbi, Marco ; Hellmann, Andrzej ; Lepretre, Stephane ; Maloisel, Frederic ; Ravandi, Farhad ; Rousselot, Philippe ; Rummel, Mathias ; Siddiqi, Tanya ; Tadmor, Tamar ; Troussard, Xavier ; Yi, Cecilia Arana ; Saglio, Giuseppe ; Roboz, Gail J. ; Balic, Kemal ; Standifer, Nathan ; He, Peng ; Marshall, Shannon ; Wilson, Wyndham ; Pastan, Ira ; Yao, Nai Shun ; Giles, Francis. / Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. In: Leukemia. 2018 ; Vol. 32, No. 8. pp. 1768-1777.
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AU - Dearden, Claire

AU - Zinzani, Pier Luigi

AU - Delgado, Julio

AU - Karlin, Lionel

AU - Robak, Tadeusz

AU - Gladstone, Douglas

AU - le Coutre, Philipp

AU - Dietrich, Sascha

AU - Gotic, Mirjana

AU - Larratt, Loree

AU - Offner, Fritz

AU - Schiller, Gary

AU - Swords, Ronan

AU - Bacon, Larry

AU - Bocchia, Monica

AU - Bouabdallah, Krimo

AU - Breems, Dimitri A.

AU - Cortelezzi, Agostino

AU - Dinner, Shira

AU - Doubek, Michael

AU - Gjertsen, Bjorn Tore

AU - Gobbi, Marco

AU - Hellmann, Andrzej

AU - Lepretre, Stephane

AU - Maloisel, Frederic

AU - Ravandi, Farhad

AU - Rousselot, Philippe

AU - Rummel, Mathias

AU - Siddiqi, Tanya

AU - Tadmor, Tamar

AU - Troussard, Xavier

AU - Yi, Cecilia Arana

AU - Saglio, Giuseppe

AU - Roboz, Gail J.

AU - Balic, Kemal

AU - Standifer, Nathan

AU - He, Peng

AU - Marshall, Shannon

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