AUTHOR=Tang Yutong , Zhou Zhenyang , Yan Han , You Yong 

TITLE=Case Report: Preemptive Treatment With Low-Dose PD-1 Blockade and Azacitidine for Molecular Relapsed Acute Myeloid Leukemia With RUNX1-RUNX1T1 After Allogeneic Hematopoietic Stem Cell Transplantation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.810284

DOI=10.3389/fimmu.2022.810284

ISSN=1664-3224

ABSTRACT=Outcomes for acute myeloid leukemia (AML) patients with hematological relapse (HR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are dismal. Measurable residual disease (MRD)-directed preemptive interventions could prevent disease progression and improve the clinical outcomes in molecular relapsed patients with warning signs of impending HR. Boosting the graft-vs-leukemia (GVL) effect by immune checkpoint inhibitors (ICIs) is an attractive prevention approach in this situation although potentially triggering graft-vs-host disease (GVHD). In the present study, we reported for the first time an AML patient with RUNX1-RUNX1T1 who underwent preemptive treatment with tislelizumab (an anti-PD-1 antibody) in combination with azacitidine to avoid HR after allo-HSCT. On day +81, the patient had a molecular relapse with an MRD depicted by RUNX1-RUN1T1-positivity (0.64%) as well as a mixed donor chimerism (94%). On day +95, with no signs of GVHD and an excellent eastern cooperative oncology group performance status (ECOG PS), the patient thus received 100 mg of azacitidine on days 1-7 subcutaneously and 100 mg of tislelizumab on day 1 intravenously. After the combination treatment, the patient achieved complete remission with complete hematologic recovery, negative MRD by flow cytometry, negative RUNX1-RUNX1T1, as well as a 100% donor chimerism. At the same time, the patient successively developed moderate immune-related adverse events (irAEs) and GVHD of the liver, lung, lower digestive tract and urinary system, which were well controlled by immunosuppressive therapies. To our knowledge, this is the first case to report the combined use of tislelizumab and azacitidine to prevent post-transplant relapse in AML. In summary, the use of ICIs in MRD positive patients presenting in hematological remission might be a promising future strategy for immune modulation to overcome the risk of HR in the post-transplant setting, but safer application schedules need to be established.