A Comparative Study Of First-and Second-line Application Of Nilotinib In Patients With Chronic Myeloid Leukemia In The Chronic Phase

Objective:To analyze the efficacy and safety of first-and second-line nilotinib treatment in patients with chronic myeloid leukemia（CML-CP）.Methods:Clinical data were retrospectively collected from December 2011 to December 2021from patients with primary diagnosis of CML-CP diagnosed and treated at the outpatient and inpatient departments of the Second Hospital of Shanxi Medical University,including gender,age,time of initial diagnosis,white blood cell count（WBC）,hemoglobin（Hb）,platelet count（PLT）,eosinophil ratio,basophil ratio,lactate dehydrogenase（LDH）,hydroxybutyrate dehydrogenase（HBDH）,BCR/ABL fusion gene level,peripheral blood primitive cell ratio,bone marrow primitive cell ratio,and spleen size at initial diagnosis.The efficacy and safety of first-line application of nilotinib and imatinib（IM）in patients with CML-CP were first compared,and then the clinical outcomes of first-line treatment and second-line conversion of nilotinib in patients with CML-CP were compared.Results:1.Comparison of the efficacy of first-line nilotinib and IM for CML-CP patients:there were 26 cases in the first-line nilotinib treatment group and 80 cases in the first-line IM treatment group.At 3 months of treatment,the CHR rate,EMR(BCR-ABL^IS<10%)rate,and BCR-ABL^IS<1%rate were 92.3%,88.0%,and 64.0%in the nilotinib group and83.8%,59.7%,and 37.1%in the IM group,respectively,and the nilotinib group was higher than the IM group（P=0.445,P=0.011,P=0.022）At 6 months,the BCR-ABL^IS<1%rate,MMR(BCR-ABL^IS<0.1%)rate,and MR4.0(BCR-ABL^IS<0.01%)rate were 86.4%,68.2%,and 36.4%in the nilotinib group and 61.7%,40.0%,and 23.3%in the IM group,respectively,and the nilotinib group was higher than the IM group（P=0.033,P=0.024,P=0.238）;the MMR rate,MR4.0 rate,and MR4.5(BCR-ABL^IS<0.0032%)rate at 12months of treatment were 84.6%,73.1%,and 34.6%in the nilotinib group and 63.6%,46.8%,and 33.8%in the IM group,respectively,and the nilotinib group was higher than the IM group（P=0.046,P=0.020,P=0.937）,and the CCy R rate at 12 months was higher in the nilotinib group than in the IM group（P=0.794）.2.comparison of the efficacy of first-line treatment with nilotinib and second-line conversion with nilotinib in patients with CML-CP:there were 26 cases in the first-line treatment group and 29 cases in the second-line conversion group.the CHR rate,EMR(BCR-ABL^IS<10%)rate,and BCR-ABL^IS<1%rate at 3 months were 92.3%,88.0%,and52.0%in the first-line treatment group,respectively,and the second-line conversion group were 86.2%,57.1%,and 42.9%,respectively,and the first-line treatment group was higher than the second-line conversion group（P=0.771,P=0.018,P=0.536）;the BCR-ABL^IS<1%rate,MMR rate,and MR4.0 rate at 6 months were 86.4%,68.2%,and 36.4%,respectively,in the first-line treatment group and 33.3%,27.8%,and 22.2%,respectively,in the second-line conversion group.27.8%,and 22.2%in the first-line treatment group than in the second-line conversion group（P=0.001,P=0.011,P=0.332）;the MMR rate,MR4.0rate,and MR4.5 rate at 12 months were 84.6%,73.1%,and 34.6%in the first-line treatment group and 44.8%,37.9%,and 17.2%in the second-line conversion group,respectively,with the first-line treatment group than the second-line conversion group（P=0.002,P=0.009,P=0.004）,and the CCy R rate at 12 months was higher in the first-line treatment group than in the second-line conversion group（P=0.205）.3.The hematological adverse reactions that occurred during nilotinib and IM treatment were mainly platelet and neutropenia and anemia,all of which were grade 1-2and could be recovered by dose reduction and discontinuation,and no grade 3-4 adverse reactions were observed.The non-hematological adverse reactions were mainly rash,pruritus,edema,myalgia,nausea,and elevated liver enzymes,all of which were tolerated and could be reduced by symptomatic treatment,with no statistically significant difference between groups（P=0.721）,with one death related to non-CML in the IM group.4.The overall survival（Overall Survival,OS）rate in this study was 100%in the nilotinib group and 98.8%in the IM group,with no statistically significant difference（P=0.576）.Conclusion:1.First-line nilotinib was more effective,and a higher proportion of CML-CP patients achieved EMR,MMR,and MR4.0.2.A higher proportion of EMR,MMR,MR4.0,and MR4.5 were obtained in the first-line nilotinib group than in the second-line conversion nilotinib group,and a deeper molecular response could be obtained with early replacement of nilotinib therapy when IM was not effective.3.The incidence of adverse reactions was similar in the nilotinib and IM groups.