Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
