Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436

Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436

We evaluate the risk, characteristics and biomarkers of treatment-emergent cytokine release syndrome (CRS) in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received APVO436 during the dose-escalation phase of a Phase 1B study (ClinicalTrials.gov...

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Autores principales: Fatih M. Uckun, Justin Watts, Alice S. Mims, Prapti Patel, Eunice Wang, Paul J. Shami, Elizabeth Cull, Cynthia Lee, Christopher R. Cogle, Tara L. Lin
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
Materias:
AML
CD123
bispecific antibody
T-cells
leukemia
clinical study
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Acceso en línea:https://doaj.org/article/06dabbe623364c4d83e5d999b62b3aa2
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spelling oai:doaj.org-article:06dabbe623364c4d83e5d999b62b3aa22021-11-11T15:27:16ZRisk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO43610.3390/cancers132152872072-6694https://doaj.org/article/06dabbe623364c4d83e5d999b62b3aa22021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5287https://doaj.org/toc/2072-6694We evaluate the risk, characteristics and biomarkers of treatment-emergent cytokine release syndrome (CRS) in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received APVO436 during the dose-escalation phase of a Phase 1B study (ClinicalTrials.gov, identifier: NCT03647800). Of four patients who developed Grade ≥ 3 CRS, two received steroid prophylaxis. The dose level, gender, race, obesity, or baseline hematologic parameters in peripheral blood did not predict the risk of CRS. Patients with a higher leukemia burden as determined by a higher total WBC, higher percentage of blasts in bone marrow, or higher percentage of blasts in peripheral blood (by hematopathology or immunophenotyping) did not have a higher incidence of CRS. There was an age difference between patients who did versus patients who did not develop CRS (72.9 ± 1.6 years (Median 73.5 years) vs. 63.3 ± 2.3 years (Median: 65.0 years), which was borderline significant (<i>p</i> = 0.04). Premedication with steroids did not eliminate the risk of CRS. Cytokine profiling in patients who developed CRS after APVO436 infusion indicates that the predominant cytokine in this inflammatory cytokine response was IL-6. APVO436-associated CRS was generally manageable with tocilizumab with or without dexamethasone. Notably, the development of CRS after APVO436 therapy did not appear to be associated with a response. The prolonged stabilization of disease, partial remissions and complete remissions were achieved in both patients who experienced CRS, as well as patients who did not experience CRS after APVO436 infusions.Fatih M. UckunJustin WattsAlice S. MimsPrapti PatelEunice WangPaul J. ShamiElizabeth CullCynthia LeeChristopher R. CogleTara L. LinMDPI AGarticleAMLCD123bispecific antibodyT-cellsleukemiaclinical studyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5287, p 5287 (2021)
institution DOAJ
collection DOAJ
language EN
topic AML
CD123
bispecific antibody
T-cells
leukemia
clinical study
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle AML
CD123
bispecific antibody
T-cells
leukemia
clinical study
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Fatih M. Uckun
Justin Watts
Alice S. Mims
Prapti Patel
Eunice Wang
Paul J. Shami
Elizabeth Cull
Cynthia Lee
Christopher R. Cogle
Tara L. Lin
Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436
description We evaluate the risk, characteristics and biomarkers of treatment-emergent cytokine release syndrome (CRS) in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who received APVO436 during the dose-escalation phase of a Phase 1B study (ClinicalTrials.gov, identifier: NCT03647800). Of four patients who developed Grade ≥ 3 CRS, two received steroid prophylaxis. The dose level, gender, race, obesity, or baseline hematologic parameters in peripheral blood did not predict the risk of CRS. Patients with a higher leukemia burden as determined by a higher total WBC, higher percentage of blasts in bone marrow, or higher percentage of blasts in peripheral blood (by hematopathology or immunophenotyping) did not have a higher incidence of CRS. There was an age difference between patients who did versus patients who did not develop CRS (72.9 ± 1.6 years (Median 73.5 years) vs. 63.3 ± 2.3 years (Median: 65.0 years), which was borderline significant (<i>p</i> = 0.04). Premedication with steroids did not eliminate the risk of CRS. Cytokine profiling in patients who developed CRS after APVO436 infusion indicates that the predominant cytokine in this inflammatory cytokine response was IL-6. APVO436-associated CRS was generally manageable with tocilizumab with or without dexamethasone. Notably, the development of CRS after APVO436 therapy did not appear to be associated with a response. The prolonged stabilization of disease, partial remissions and complete remissions were achieved in both patients who experienced CRS, as well as patients who did not experience CRS after APVO436 infusions.
format article
author Fatih M. Uckun
Justin Watts
Alice S. Mims
Prapti Patel
Eunice Wang
Paul J. Shami
Elizabeth Cull
Cynthia Lee
Christopher R. Cogle
Tara L. Lin
author_facet Fatih M. Uckun
Justin Watts
Alice S. Mims
Prapti Patel
Eunice Wang
Paul J. Shami
Elizabeth Cull
Cynthia Lee
Christopher R. Cogle
Tara L. Lin
author_sort Fatih M. Uckun
title Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436
title_short Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436
title_full Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436
title_fullStr Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436
title_full_unstemmed Risk, Characteristics and Biomarkers of Cytokine Release Syndrome in Patients with Relapsed/Refractory AML or MDS Treated with CD3xCD123 Bispecific Antibody APVO436
title_sort risk, characteristics and biomarkers of cytokine release syndrome in patients with relapsed/refractory aml or mds treated with cd3xcd123 bispecific antibody apvo436
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/06dabbe623364c4d83e5d999b62b3aa2
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