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Minimal residual hairy cell leukemia eradication with moxetumomab pasudotox: phase 1 results and long-term follow-up.

Authors
  • Kreitman, Robert J1
  • Tallman, Martin S2
  • Robak, Tadeusz3
  • Coutre, Steven4
  • Wilson, Wyndham H5
  • Stetler-Stevenson, Maryalice6
  • FitzGerald, David J1
  • Santiago, Linda7
  • Gao, Guozhi7
  • Lanasa, Mark C7
  • Pastan, Ira1
  • 1 Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  • 2 Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.
  • 3 Department of Haematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland. , (Poland)
  • 4 Division of Hematology, Stanford University School of Medicine, Stanford, CA.
  • 5 Metabolism Branch and.
  • 6 Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD; and.
  • 7 MedImmune, Gaithersburg, MD.
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
May 24, 2018
Volume
131
Issue
21
Pages
2331–2334
Identifiers
DOI: 10.1182/blood-2017-09-803072
PMID: 29487070
Source
Medline
Language
English
License
Unknown

Abstract

Anti-CD22 moxetumomab pasudotox achieved 46% complete remissions (CRs) in previously reported phase 1 testing in relapsed/refractory hairy cell leukemia (HCL; n = 28). The importance of minimal residual disease (MRD) after CR in HCL is unknown. A 21-patient extension cohort received 50 µg/kg every other day for 3 doses in 4-week cycles. These patients plus 12 previously reported at this upper dose level received 143 cycles without dose-limiting toxicity. The combined 33-patient cohort achieved 64% CR and 88% overall response rates, with median CR duration of 42.4 months. Of 32 50-µg/kg patients evaluable for MRD by bone marrow aspirate flow cytometry (most stringent assessment), median CR duration was 13.5 (4.9-42.4) months in 9 MRD-positive CRs vs 42.1 (24.0-69.2) months in 11 MRD-negative CRs (P < .001). Among MRD-negative CRs, 10 patients had ongoing CR, 9 without MRD, at end of study. To our knowledge, moxetumomab pasudotox is the only nonchemotherapy regimen that can eliminate MRD in a significant percentage of HCL patients, to enhance CR duration. Repeated dosing, despite early neutralizing antibodies, increased active drug levels without detectable toxicity from immunogenicity. The activity and safety profiles of moxetumomab pasudotox support ongoing phase 3 testing in HCL. This trial was registered at www.clinicaltrials.gov as #NCT00586924.

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