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Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia.
Goswami, Meghali; Gui, Gege; Dillon, Laura W; Lindblad, Katherine E; Thompson, Julie; Valdez, Janet; Kim, Dong-Yun; Ghannam, Jack Y; Oetjen, Karolyn A; Destefano, Christin B; Smith, Dana M; Tekleab, Hanna; Li, Yeusheng; Dagur, Pradeep; Hughes, Thomas; Marté, Jennifer L; Del Rivero, Jaydira; Klubo-Gwiezdzinksa, Joanna; Gulley, James L; Calvo, Katherine R; Lai, Catherine; Hourigan, Christopher S.
Afiliación
  • Goswami M; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Gui G; National Cancer Institute, Bethesda, Maryland, USA.
  • Dillon LW; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Lindblad KE; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Thompson J; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Valdez J; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Kim DY; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Ghannam JY; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Oetjen KA; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Destefano CB; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Smith DM; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Tekleab H; Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
  • Li Y; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Dagur P; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Hughes T; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
  • Marté JL; National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
  • Del Rivero J; National Cancer Institute, Bethesda, Maryland, USA.
  • Klubo-Gwiezdzinksa J; National Cancer Institute, Bethesda, Maryland, USA.
  • Gulley JL; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA.
  • Calvo KR; National Cancer Institute, Bethesda, Maryland, USA.
  • Lai C; National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
  • Hourigan CS; National Heart Lung and Blood Institute, Bethesda, Maryland, USA.
J Immunother Cancer ; 10(1)2022 01.
Article en En | MEDLINE | ID: mdl-35017151
BACKGROUND: The powerful 'graft versus leukemia' effect thought partly responsible for the therapeutic effect of allogeneic hematopoietic cell transplantation in acute myeloid leukemia (AML) provides rationale for investigation of immune-based therapies in this high-risk blood cancer. There is considerable preclinical evidence for potential synergy between PD-1 immune checkpoint blockade and the hypomethylating agents already commonly used for this disease. METHODS: We report here the results of 17 H-0026 (PD-AML, NCT02996474), an investigator sponsored, single-institution, single-arm open-label 10-subject pilot study to test the feasibility of the first-in-human combination of pembrolizumab and decitabine in adult patients with refractory or relapsed AML (R-AML). RESULTS: In this cohort of previously treated patients, this novel combination of anti-PD-1 and hypomethylating therapy was feasible and associated with a best response of stable disease or better in 6 of 10 patients. Considerable immunological changes were identified using T cell receptor ß sequencing as well as single-cell immunophenotypic and RNA expression analyses on sorted CD3+ T cells in patients who developed immune-related adverse events (irAEs) during treatment. Clonal T cell expansions occurred at irAE onset; single-cell sequencing demonstrated that these expanded clones were predominately CD8+ effector memory T cells with high cell surface PD-1 expression and transcriptional profiles indicative of activation and cytotoxicity. In contrast, no such distinctive immune changes were detectable in those experiencing a measurable antileukemic response during treatment. CONCLUSION: Addition of pembrolizumab to 10-day decitabine therapy was clinically feasible in patients with R-AML, with immunological changes from PD-1 blockade observed in patients experiencing irAEs.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Protocolos de Quimioterapia Combinada Antineoplásica / Anticuerpos Monoclonales Humanizados / Decitabina / Inmunoterapia Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Immunother Cancer Año: 2022 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Protocolos de Quimioterapia Combinada Antineoplásica / Anticuerpos Monoclonales Humanizados / Decitabina / Inmunoterapia Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Immunother Cancer Año: 2022 Tipo del documento: Article