Clinical Efficacy Observation Of First-line And Second-line Treatment With Nilotinib In Chronic Myeloid Leukemia

Objective:To observe the clinical efficacy of nilotinib as the first-line and second-line treatment in patients with chronic myeloid leukemia（CML-CP）,and to further discuss the best time to use the second-generation tyrosine kinase inhibitor.Methods:Retrospective analysis of the patients with CML-CP diagnosed and treated in our hospital from June 1,2014 to December 31,2019.The gender,age,initial diagnosis time,TKI initial treatment time and second generation conversion time,white blood cell count（WBC）,absolute value of basophil,hemoglobin（Hg）,platelet count（PLT）,BCR/ABL fusion gene level,The proportion of bone marrow primordial cells were collected.There were 219 patients,127 males and 92 females,with a median age of 44.There were 58 CML patients treated with first-line nilotinib and 161 CML patients treated with first-line imatinib.Fifty eight CML patients were treated with second-generation TKI nilotinib in the first line,and 57 CML patients were treated with second-line conversion to nilotinib.Starting from the time of imatinib treatment,the patients in the second-line application of nilotinib group were divided into early conversion group（≤6 months）（group A）and late conversion group（>6 months）（group B）according to the conversion time,including 40 cases in group A and 17 cases in group B.The curative effect after conversion treatment was compared.Results:1.Comparison of the efficacy of imatinib treatment with that of firs t-line nimotinib in CML-CP patients:58 CML-CP patients were selected for the nilotinib treatment at the initial diagnosis,161 patients in the firs t generation TKI imatinib group were selected.The EMR(BCR-ABL^IS≤10%)and BCR-ABL^IS≤1%、BCR-ABL^IS≤0.1%（MMR）were obtained in t he first three months,all of them were higher than that in imatinib grou p（93.1%vs 62.1%,69.0%vs 32.9%,39.7%vs 11.2%）,and they were statistically significant（P<0.001,P<0.001,P=0.001）;After 6 months of trea tment,the proportion of patients in the nilotinib group was higher than t hat in imatinib group（86.2%vs 60.9%,65.5%vs 21.7%）,and they wer e statistically significant（P<0.001）.The rate of patients in the nilotinib t reatment group with MMR、BCR-ABL^IS≤0.01%（MR4.0）and BCR-ABL^IS≤0.0032%（MR4.5）in 12 months was higher than that in imatinib group（81.0%vs 41.6%,67.2%vs 39.8%,63.8%vs 37.9%）,with statistical di fferences（P<0.001,P<0.001,P=0.001）.2.The curative effect of first-line nilotinib treatment and second-line nilotinib conversion treatment for CML-CP patients:58 patients（group A）,57patients with imatinib conversion of nilotinib（group B）.The rates of BCR-ABL^IS≤10%and BCR-ABL^IS≤1%in the two groups at 3 months of treatment were compared,which were higher in group A than those in group B（93.1%vs 86.0%,69.0%vs 64.9%）,the rates of MMR in the two groups at 3months were 39.7%and 47.4%.There was no significant difference between the two groups（P=0.211,P=0.644,P=0.404）;The rates of BCR-ABL^IS≤1%and MMR in group A were higher than those in group B（86.2%vs 78.9%and65.5%vs 59.6%）.There was no significant difference between the two groups（P=0.304,P=0.561）;After 12 months of treatment,the rates of MMR、MR4.0and MR4.5 in group A were higher than those in group B（81.0%vs 71.9%,67.2%vs 54.4%,63.8%vs 52.6%）.There was no significant difference between the two groups（P=0.249,P=0.158,P=0.225）.3.The curative effect of the early and late conversion groups of th e second-line nilotinib was compared:57 patients with imatinib conversio n to second-line nilotinib were divided into early conversion group（gro up A）and advanced conversion group（group B）.After conversion treatm ent,the percentages of BCR-ABL^IS≤10%in group A and B at 3 month s were 87.5%and 82.4%,and the percentages of BCR-ABL^IS≤1%in gr oup A and B were 62.5%and 70.6%,respectively.There was no statist ical difference between the two groups（P=0.924,P=0.558）.The proporti on of patients with MMR at 3 months in group A was higher than that in group B（50.0%vs17.6%）,and the comparison between the two grou ps was statistically significant（P=0.023）.The proportion of patients wit h BCR-ABL^IS≤1%and MMR at 6 months in group A was higher than that in group B（82.5%vs70.6%and 62.5%vs47.1%）,and there was no statistical difference between the two groups（P=0.513,P=0.280）.The pro portion of patients with MMR、MR4.0 and MR4.5 at 12 months in gro up A was higher than that in group B（72.5%vs 64.7%,60.0%vs 47.1%,57.5%vs 41.2%）.There was no statistical significance between the two groups（P=0.556,P=0.368,P=0.259）.Conclusion:1.The second generation TKI first-line treatment of CML patients is better than imatinib first-line treatment of CML patients,a higher proportion of patients get EMR and MR4.5.2.The proportion of EMR and MR4.5 in the first-line nilotinib group was higher than that in the second-line nilotinib group,but there was no statistical difference,suggesting that the sample size should be further expanded to evaluate the efficacy.3.CML patients treated with first-line imatinib who failed to reach treatment goals were more likely to achieve MMR at 3 months after early conversion（within 6 months）to second-generation TKI.