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Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia.

Authors
  • Gökbuget, Nicola1
  • Dombret, Hervé2
  • Bonifacio, Massimiliano3
  • Reichle, Albrecht4
  • Graux, Carlos5
  • Faul, Christoph6
  • Diedrich, Helmut7
  • Topp, Max S8
  • Brüggemann, Monika9
  • Horst, Heinz-August9
  • Havelange, Violaine10
  • Stieglmaier, Julia11
  • Wessels, Hendrik11
  • Haddad, Vincent12
  • Benjamin, Jonathan E13
  • Zugmaier, Gerhard11
  • Nagorsen, Dirk13
  • Bargou, Ralf C14
  • 1 University Hospital, Frankfurt, Germany. , (Germany)
  • 2 University Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France. , (France)
  • 3 Department of Medicine, Section of Hematology, Verona University, Verona, Italy. , (Italy)
  • 4 University Hospital Regensburg, Regensburg, Germany. , (Germany)
  • 5 Université Catholique de Louvain, CHU UCL Namur (Godinne), Yvoir, Belgium. , (Belgium)
  • 6 University Hospital and Comprehensive Cancer Center Tübingen, Universitätsklinikum Tübingen, Tübingen, Germany. , (Germany)
  • 7 Department of Hematology and Oncology, Medizinische Hochschule, Hannover, Germany. , (Germany)
  • 8 Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany. , (Germany)
  • 9 Klinik für Innere Medizin II, Universitätsklinikum Schleswig-Holstein, Kiel, Germany. , (Germany)
  • 10 Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium. , (Belgium)
  • 11 Amgen Research (Munich), GmbH, Munich, Germany. , (Germany)
  • 12 Amgen, Ltd., Cambridge, United Kingdom. , (United Kingdom)
  • 13 Amgen, Inc., Thousand Oaks, CA; and.
  • 14 Comprehensive Cancer Center Mainfranken, Uniklinikum Würzburg, Würzburg, Germany. , (Germany)
Type
Published Article
Journal
Blood
Publisher
American Society of Hematology
Publication Date
Apr 05, 2018
Volume
131
Issue
14
Pages
1522–1531
Identifiers
DOI: 10.1182/blood-2017-08-798322
PMID: 29358182
Source
Medline
Language
English
License
Unknown

Abstract

Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission after multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase-polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10-3) received blinatumomab 15 µg/m2 per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1. The primary end point was complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients achieved a complete MRD response. In the subgroup of 110 patients with Ph-negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5 months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7 months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, a majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders. This study is registered at www.clinicaltrials.gov as #NCT01207388. © 2018 by The American Society of Hematology.

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