{"doi":"10.1136/jitc-2021-003392","title":"Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia","abstract":"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 β 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.","journal":"Journal for ImmunoTherapy of Cancer","year":2022,"id":235656,"datarank":2.0814201266869965,"base_score":4.356708826689592,"endowment":4.356708826689592,"self_citation_contribution":0.6535063240034389,"citation_network_contribution":1.4279138026835574,"self_endowment_contribution":0.6535063240034389,"citer_contribution":1.4279138026835574,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":74,"citers_with_citation_signal":67,"citers_with_endowment":67,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02996474"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":351427,"name":"Gege Gui","orcid":"0000-0002-4141-183X","position":1,"is_corresponding":false},{"id":218235,"name":"Laura W. Dillon","orcid":"0000-0002-4877-9354","position":2,"is_corresponding":false},{"id":31275,"name":"Katherine E. Lindblad","orcid":"0000-0001-6093-5578","position":3,"is_corresponding":false},{"id":351429,"name":"Julie Thompson","orcid":"0000-0002-2361-1707","position":4,"is_corresponding":false},{"id":335255,"name":"Janet Valdez","orcid":"0000-0003-1913-4781","position":5,"is_corresponding":false},{"id":268912,"name":"Dong‐Yun Kim","orcid":"0000-0001-9405-4840","position":6,"is_corresponding":false},{"id":314729,"name":"Jack Ghannam","orcid":"0000-0003-0275-9099","position":7,"is_corresponding":false},{"id":563333,"name":"Karolyn A. Oetjen","orcid":"0000-0002-2846-8831","position":8,"is_corresponding":false},{"id":351428,"name":"Christin B. DeStefano","orcid":"0000-0002-8890-7760","position":9,"is_corresponding":false},{"id":658322,"name":"Dana M. Smith","orcid":"0000-0001-5410-0400","position":10,"is_corresponding":false},{"id":810809,"name":"Hanna Tekleab","orcid":null,"position":11,"is_corresponding":false},{"id":855369,"name":"Yeusheng Li","orcid":null,"position":12,"is_corresponding":false},{"id":855370,"name":"Pradeep Dagur","orcid":null,"position":13,"is_corresponding":false},{"id":320682,"name":"Thomas E. Hughes","orcid":"0000-0003-0554-427X","position":14,"is_corresponding":false},{"id":257287,"name":"Jennifer L. Marté","orcid":null,"position":15,"is_corresponding":false},{"id":302291,"name":"Jaydira Del Rivero","orcid":"0000-0001-9710-4030","position":16,"is_corresponding":false},{"id":810810,"name":"Joanna Klubo-Gwiezdzinksa","orcid":null,"position":17,"is_corresponding":false},{"id":239942,"name":"James L. Gulley","orcid":"0000-0002-6569-2912","position":18,"is_corresponding":false},{"id":218270,"name":"Katherine R. 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