AUTHOR=Yao Sun , Jianlin Chen , Zhuoqing Qiao , Yuhang Li , Jiangwei Hu , Guoliang Hu , Hongmei Ning , Bin Zhang , Liangding Hu 

TITLE=Case Report: Combination Therapy With PD-1 Blockade for Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation Resulted in Fatal GVHD

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.639217

DOI=10.3389/fimmu.2021.639217

ISSN=1664-3224

ABSTRACT=Background: Azacitidine is commonly used in the treatment of relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MSD), after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the effectiveness of monotherapy is still very low. A possible mechanism of resistance to hypomethylating agents (HMAs) is the upregulation of the expression of inhibitory checkpoint receptors and its ligands, making the combination of HMAs and immune checkpoint blockage therapy a rational approach. Although the safety of anti-programmed cell death protein (PD)-1 antibodies for patients with post-allo-HSCT remains a complicated issue, the preliminary clinical result of combining azacitidine with anti-PD-1 antibodies is encouraging; however, the safety and efficacy of this approach need further investigation.
Case Presentation: We report the case of treated secondary (ts)-AML in a patient who received tislelizumab (an anti-PD-1 antibody) in combination with azacitidine. The patient relapsed after allo-HSCT, and was previously exposed to HMAs-based therapy. He received tislelizumab as compassionate use. After combined treatment, the patient achieved complete remission with incomplete hematologic recovery, negative minimal residual disease by flow cytometry, and negative Wilm’s Tumor protein (WT) 1. However, he successively developed serious immune-related adverse events and graft versus host disease (GVHD), and eventually died from the complications of GVHD. 
Conclusion: To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to treat relapsed AML post-transplantation. Our report highlights the safety concerns of anti-PD-1 antibody combined with azacitidine, after allo-HSCT, especially the risk of GVHD, and provides basis for future studies.