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Pembrolizumab and decitabine for refractory or relapsed acute myeloid leukemia

Goswami M, Gui G, Dillon LW, Lindblad KE, Thompson J, Valdez J, Kim DY, Ghannam JY, Oetjen KA, Destefano CB, Smith DM, Tekleab H, Li Y, Dagur P, Hughes T, Marté JL, Del Rivero J, Klubo-Gwiezdzinksa J, Gulley JL, Calvo KR, Lai C, Hourigan CS,
Journal for ImmuoTherapy of Cancer Jan 2022

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.




Institution Type


Indication / Modality

Acute Myleoid Leukemia (AML)

Goal of Study

Clonal Heterogeneity, Tumor Profiling, CHIP

Key Genes


PAD Project


Analytes Assessed

CNV, InDels, Extracellular Protein, SNV

Sample Storage

Fresh Frozen

Sample Prep

Whole Cells

Sample Type

Patient Material

Tissue / Organ

Bone Marrow Aspirates



Panel Used


Proof Point Demonstrated

Clonality, Co-occurrence, Cell Identity, Better than Bulk, Multi-omics