Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia

• DOI: 10.1136/jitc-2021-003392
• Publication Date: 2022-01-11T16:36:43Z
• Authors: Meghali Goswami; Gege Gui; Laura W Dillon; Katherine E Lindblad; Julie Thompson; Janet Valdez; Dong-Yun Kim; Jack Y Ghannam; Karolyn A Oetjen; Christin B Destefano; Dana M Smith; Hanna Tekleab; Yeusheng Li; Pradeep Dagur; Thomas Hughes; Jennifer L Marté; Jaydira del Rivero; Joanna Klubo-Gwie...; James L Gulley; Katherine R Calvo; Catherine Lai; Christopher S Hou...
• Keywords: Decitabine; Azacitidine; Hypomethylating agent; Immune checkpoint

Background The powerful ‘graft versus leukemia’ effect thought partly responsible for the therapeutic of allogeneic hematopoietic cell transplantation in acute myeloid leukemia (AML) provides rationale investigation immune-based therapies this high-risk blood cancer. There is considerable preclinical evidence potential synergy between PD-1 immune checkpoint blockade and hypomethylating agents already commonly used disease. Methods We report here results 17 H-0026 (PD-AML, NCT02996474 ), an investigator sponsored, single-institution, single-arm open-label 10-subject pilot study to test feasibility first-in-human combination pembrolizumab decitabine adult patients with refractory or relapsed AML (R-AML). Results In cohort previously treated patients, novel anti-PD-1 therapy was feasible associated a best response stable disease better 6 10 patients. Considerable immunological changes were identified using T receptor β sequencing as well single-cell immunophenotypic RNA expression analyses on sorted CD3+ cells who developed immune-related adverse events (irAEs) during treatment. Clonal expansions occurred at irAE onset; demonstrated that these expanded clones predominately CD8+ effector memory high surface transcriptional profiles indicative activation cytotoxicity. contrast, no such distinctive detectable those experiencing measurable antileukemic Conclusion Addition 10-day clinically R-AML, from observed irAEs.