PMID- 34185931 OWN - NLM STAT- MEDLINE DCOM- 20210914 LR - 20230920 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 112 IP - 9 DP - 2021 Sep TI - Low-dose decitabine plus venetoclax is safe and effective as post-transplant maintenance therapy for high-risk acute myeloid leukemia and myelodysplastic syndrome. PG - 3636-3644 LID - 10.1111/cas.15048 [doi] AB - Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high-risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative option for patients suffering from high-risk AML/MDS. However, many patients relapse after allo-HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL-2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft-versus-host disease (GVHD) and boost the graft-versus-leukemia (GVL) effect post-transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low-dose decitabine (LDEC) plus VEN to prevent relapse after allo-HSCT for high-risk AML/MDS patients. Twenty patients with high-risk AML (n = 17) or high-risk MDS (n = 3) post-transplantation were recruited. Approximately day 100 post-transplantation, all patients received LDEC (15 mg/m(2) for 3 d) followed by VEN (200 mg) on d 1-21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event-free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo-HSCT. Survival outcomes were assessed using Kaplan-Meier analysis. The median follow-up was 598 (149-1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2-y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2-y EFS time was 525 (149-1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo-HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high-risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high-risk AML/MDS patients. CI - (c) 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Wei, Yunxiong AU - Wei Y AUID- ORCID: 0000-0003-0088-7775 AD - The First Central Clinical College of Tianjin Medical University, Tianjin, China. FAU - Xiong, Xia AU - Xiong X AD - The First Central Clinical College of Tianjin Medical University, Tianjin, China. FAU - Li, Xin AU - Li X AD - The First Central Clinical College of Tianjin Medical University, Tianjin, China. FAU - Lu, Wenyi AU - Lu W AD - Department of Hematology, Tianjin First Central Hospital, Tianjin, China. FAU - He, Xiaoyuan AU - He X AD - Department of Hematology, Tianjin First Central Hospital, Tianjin, China. FAU - Jin, Xin AU - Jin X AD - Nankai University School of Medicine, Tianjin, China. FAU - Sun, Rui AU - Sun R AD - Nankai University School of Medicine, Tianjin, China. FAU - Lyu, Hairong AU - Lyu H AD - Department of Hematology, Tianjin First Central Hospital, Tianjin, China. FAU - Yuan, Ting AU - Yuan T AD - Department of Hematology, Tianjin First Central Hospital, Tianjin, China. FAU - Sun, Tongtong AU - Sun T AD - Department of Radiology, First Central Clinical College, Tianjin Medical University, Tianjin, China. FAU - Zhao, Mingfeng AU - Zhao M AUID- ORCID: 0000-0002-5995-7558 AD - Department of Hematology, Tianjin First Central Hospital, Tianjin, China. LA - eng GR - 20YFZCSY00800/Tianjin Municipal Science and Technology Bureau/ GR - 81800105/National Natural Science Foundation of China/ GR - 81970180/National Natural Science Foundation of China/ GR - 2019YJSS177/Tianjin Research Innovation Project for Postgraduate Students/ PT - Journal Article DEP - 20210721 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Antimetabolites, Antineoplastic) RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Sulfonamides) RN - 776B62CQ27 (Decitabine) RN - N54AIC43PW (venetoclax) SB - IM MH - Adult MH - Aged MH - Antimetabolites, Antineoplastic/administration & dosage/*adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects MH - Bridged Bicyclo Compounds, Heterocyclic/administration & dosage/*adverse effects MH - Decitabine/administration & dosage/*adverse effects MH - Female MH - Follow-Up Studies MH - Hematopoietic Stem Cell Transplantation/*adverse effects MH - Humans MH - Leukemia, Myeloid, Acute/*drug therapy/*surgery MH - Male MH - Middle Aged MH - Myelodysplastic Syndromes/*drug therapy/*surgery MH - Progression-Free Survival MH - Prospective Studies MH - Recurrence MH - Sulfonamides/administration & dosage/*adverse effects MH - Transplantation Conditioning/*methods MH - Transplantation, Homologous/adverse effects MH - Young Adult PMC - PMC8409404 OTO - NOTNLM OT - Venetoclax OT - allo-HSCT OT - decitabine OT - maintence therapy COIS- The authors declare no conflicts of interest related to this work. EDAT- 2021/06/30 06:00 MHDA- 2021/09/15 06:00 PMCR- 2021/09/01 CRDT- 2021/06/29 17:24 PHST- 2021/06/22 00:00 [revised] PHST- 2021/03/27 00:00 [received] PHST- 2021/06/24 00:00 [accepted] PHST- 2021/06/30 06:00 [pubmed] PHST- 2021/09/15 06:00 [medline] PHST- 2021/06/29 17:24 [entrez] PHST- 2021/09/01 00:00 [pmc-release] AID - CAS15048 [pii] AID - 10.1111/cas.15048 [doi] PST - ppublish SO - Cancer Sci. 2021 Sep;112(9):3636-3644. doi: 10.1111/cas.15048. Epub 2021 Jul 21.