Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomab
Corresponding Author
Rosemary Sutton
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Correspondence
Rishi Kotecha, Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.
Email: [email protected],
Rosemary Sutton, Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia.
Email: [email protected]
Search for more papers by this authorLuciano Dalla Pozza
Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
Search for more papers by this authorSeong Lin Khaw
Children's Cancer Centre, The Royal Children's Hospital, Melbourne, Victoria, Australia
Search for more papers by this authorChris Fraser
Blood and Bone Marrow Transplant Program, Queensland Children's Hospital, Brisbane, Queensland, Australia
Search for more papers by this authorTom Revesz
Department of Clinical Haematology and Oncology, Women's and Children's Hospital, Adelaide, South Australia, Australia
University of Adelaide, Adelaide, South Australia, Australia
Search for more papers by this authorJanis Chamberlain
John Hunter Children's Hospital, Newcastle, New South Wales, Australia
Search for more papers by this authorRichard Mitchell
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
Search for more papers by this authorToby N. Trahair
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
Search for more papers by this authorCaroline M. Bateman
Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
Search for more papers by this authorNicola C. Venn
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
Search for more papers by this authorTamara Law
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
Search for more papers by this authorErika Ong
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
Search for more papers by this authorSusan L. Heatley
University of Adelaide, Adelaide, South Australia, Australia
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Search for more papers by this authorBarbara J. McClure
University of Adelaide, Adelaide, South Australia, Australia
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Search for more papers by this authorClaus Meyer
Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia, Goethe University, Frankfurt, Germany
Search for more papers by this authorRolf Marschalek
Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia, Goethe University, Frankfurt, Germany
Search for more papers by this authorMichelle J. Henderson
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Search for more papers by this authorSiobhan Cross
Children's Haematology/Oncology Centre, Christchurch Hospital, Christchurch, New Zealand
Search for more papers by this authorDeborah L. White
University of Adelaide, Adelaide, South Australia, Australia
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Australian Genomics Health Alliance, Parkville, Melbourne, Victoria, Australia
Search for more papers by this authorCorresponding Author
Rishi S. Kotecha
Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia
Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Western Australia, Australia
Correspondence
Rishi Kotecha, Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.
Email: [email protected],
Rosemary Sutton, Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Rosemary Sutton
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Correspondence
Rishi Kotecha, Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.
Email: [email protected],
Rosemary Sutton, Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia.
Email: [email protected]
Search for more papers by this authorLuciano Dalla Pozza
Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
Search for more papers by this authorSeong Lin Khaw
Children's Cancer Centre, The Royal Children's Hospital, Melbourne, Victoria, Australia
Search for more papers by this authorChris Fraser
Blood and Bone Marrow Transplant Program, Queensland Children's Hospital, Brisbane, Queensland, Australia
Search for more papers by this authorTom Revesz
Department of Clinical Haematology and Oncology, Women's and Children's Hospital, Adelaide, South Australia, Australia
University of Adelaide, Adelaide, South Australia, Australia
Search for more papers by this authorJanis Chamberlain
John Hunter Children's Hospital, Newcastle, New South Wales, Australia
Search for more papers by this authorRichard Mitchell
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
Search for more papers by this authorToby N. Trahair
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Kids Cancer Centre, Sydney Children's Hospital, Randwick, New South Wales, Australia
Search for more papers by this authorCaroline M. Bateman
Cancer Centre for Children, The Children's Hospital at Westmead, Sydney, New South Wales, Australia
Search for more papers by this authorNicola C. Venn
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
Search for more papers by this authorTamara Law
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
Search for more papers by this authorErika Ong
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
Search for more papers by this authorSusan L. Heatley
University of Adelaide, Adelaide, South Australia, Australia
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Search for more papers by this authorBarbara J. McClure
University of Adelaide, Adelaide, South Australia, Australia
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Search for more papers by this authorClaus Meyer
Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia, Goethe University, Frankfurt, Germany
Search for more papers by this authorRolf Marschalek
Institute of Pharmaceutical Biology/Diagnostic Center of Acute Leukemia, Goethe University, Frankfurt, Germany
Search for more papers by this authorMichelle J. Henderson
Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia
School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
Search for more papers by this authorSiobhan Cross
Children's Haematology/Oncology Centre, Christchurch Hospital, Christchurch, New Zealand
Search for more papers by this authorDeborah L. White
University of Adelaide, Adelaide, South Australia, Australia
Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
Australian Genomics Health Alliance, Parkville, Melbourne, Victoria, Australia
Search for more papers by this authorCorresponding Author
Rishi S. Kotecha
Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia
Telethon Kids Cancer Centre, Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
School of Pharmacy and Biomedical Sciences, Curtin University, Perth, Western Australia, Australia
Correspondence
Rishi Kotecha, Department of Clinical Haematology, Oncology and Bone Marrow Transplantation, Perth Children's Hospital, Perth, Western Australia, Australia.
Email: [email protected],
Rosemary Sutton, Molecular Diagnostics, Children's Cancer Institute, Sydney, New South Wales, Australia.
Email: [email protected]
Search for more papers by this authorAbstract
We report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (B-ALL) and high-risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2-year progression-free survival (PFS) of 39% and 2-year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8). Four patients successfully received CD19-directed chimeric antigen receptor T-cell therapy despite prior blinatumomab exposure. Inferior 2-year PFS was associated with MRD positivity (20%, n = 15) and in KMT2A-rearranged infants (15%, n = 9). Our findings highlight that not all children with relapsed/refractory B-ALL respond to blinatumomab and factors such as blast genotype may affect prognosis.
CONFLICT OF INTEREST
AMGEN provided blinatumomab for most patients on a compassionate basis but played no part in design or analysis of this study and imposed no conditions on publication. All authors declare that they have no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| pbc28922-sup-0001-FigureS1.pdf59.2 KB | Figure S1 CONSORT diagram for patient selection |
| pbc28922-sup-0002-FigureS2.pdf43.2 KB | Figure S2 Kaplan–Meier survival curves showing (A) progression-free and overall survival (OS) of entire cohort, (B) OS according to clinical indication for blinatumomab, and (C) OS according to minimal residual disease (MRD) status and clinical indication |
| pbc28922-sup-0003-FigureS3.pdf317.2 KB | Figure S3 Minimal residual disease (MRD) response to blinatumomab of entire cohort |
| pbc28922-sup-0004-FigureS4.pdf1.9 MB | Figure S4 Individual patient minimal residual disease (MRD) response with time according to treatment administered |
| pbc28922-sup-0005-TableS1.pdf99.9 KB | Supplementary Table S1 Patient characteristics, acute lymphoblastic leukaemia (ALL) subtype and cytogenetics |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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