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Effect of Ado-Trastuzumab Emtansine on Autologous Platelet Kinetics and Function.
Ansary, Ali M; Stolla, Moritz; Corson, Jill; Cundy, Arianne; Bailey, S Lawrence; Pellham, Esther; Bawcom-Randall, Morgan; Slichter, Sherrill J; Gadi, Vijayakrishna K.
Afiliação
  • Ansary AM; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
  • Stolla M; Division of Hematology, Department of Medicine, University of Washington Medical Center, Seattle, WA.
  • Corson J; Bloodworks Northwest Research Institute, Seattle, WA.
  • Cundy A; Bloodworks Northwest Research Institute, Seattle, WA.
  • Bailey SL; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
  • Pellham E; Bloodworks Northwest Research Institute, Seattle, WA.
  • Bawcom-Randall M; Bloodworks Northwest Research Institute, Seattle, WA.
  • Slichter SJ; Bloodworks Northwest Research Institute, Seattle, WA.
  • Gadi VK; Division of Hematology, Department of Medicine, University of Washington Medical Center, Seattle, WA.
JCO Precis Oncol ; 6: e2200237, 2022 Sep.
Article em En | MEDLINE | ID: mdl-36108260
ABSTRACT

PURPOSE:

Ado-trastuzumab emtansine (T-DM1) treatment results in grade 3-4 thrombocytopenia in 8%-13% of patients. Prior in vitro studies reported T-DM1 inhibition of megakaryocyte maturation as the cause of decreased platelet production. The current observational study was initiated to evaluate causes of thrombocytopenia in patients with metastatic breast cancer. MATERIALS AND

METHODS:

Patients with human epidermal growth factor receptor 2-positive metastatic breast cancer (N = 11) were enrolled in this postmarket safety study. 111-Indium- radiolabeled autologous platelet recoveries and survivals as well as serial platelet counts, bleeding time assays, and platelet aggregation responses to a wide range of agonists were performed at baseline (BL) and during two consecutive cycles of the drug (3.6 mg/kg IV once every 3 weeks).

RESULTS:

Platelet nadirs occurred earlier in cycle 2 than in cycle 1. Average nadir counts (% BL) in cycles 1 and 2 were 116,000/µL (53% ± 6%) and 115,000/µL (51% ± 9%), respectively, with return to BL by D15 in both cycles. BL platelet survival averaged 8.8 (± 0.3) days but progressively shortened to 5.5 (± 0.5) days during cycle 1 and to 4.6 (± 0.3) days during cycle 2 (P < .001 compared with BL for both cycles). Aggregation responses to all agonists decreased during the study, both in cycle 1 and cycle 2.

CONCLUSION:

Following T-DM1 administration, we observed statistically significant progressive decreases in platelet survivals and decreased platelet function from BL values. In distinction to published in vitro studies, these unexpected results indicate a direct toxic effect of T-DM1 on patients' autologous circulating platelets.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombocitopenia / Neoplasias da Mama / Maitansina Tipo de estudo: Observational_studies Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trombocitopenia / Neoplasias da Mama / Maitansina Tipo de estudo: Observational_studies Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article