| Objective To evaluate the efficacy and safety of nilotinib as a second-line therapy in the treatment-failure in patients with chronic myelocytic leukemia in chronic phase(CML-CP),and to explore the optimal time for tyrosine kinase inhibitor type transition.Methods A retrospective comparison and analysis were conducted on 87 patients with CML-CP with imatinib treatment-failure until December 31,2016,who were diagnosed in 12 hospitals of Province Guangdong and Province Hainan from January 1,2012 to December 31,2013.According to whether the second generation TKI was replaced after IM treatment-failure and the time of replacement,it was divided into three groups,which were early switch to alternate group(the alternation time was less than 6 months for IM treatment failure),late switch to alternate group(the alternation time was more than 6 months for IM treatment failure)and non-switch to alternate group(continue to use IM treatment).The clinical characteristics were analyzed with the changes in cytobiology,cytogenetics,BCR-ABL fusion gene m RNA level,adverse reactions and long-time survival of the patients before treatment and after 3 months,6months and 12 months of treatment among three groups.Numerical variables were described by median(range),which was analyzed by non-parametric rank and kruskal-wallis tests between groups,and nemenyi test was used for further pairwise comparison.Qualitative variables were described by proportion(rate),which was analyzed by chi-square test or Fisher’s exact test.The probabilities of the event free survival time(EFS),the progression free survival time(PFS)and the total survival time(OS)were calculated by using the Kaplan-Meier method and analyzed by log-rank test.All the statistical data were analyzed by SPSS 21.0(IBM,NY,USA)software.When the bilateral p value was < 0.05,the difference was confirmed as statistically significant difference,and the bilateral p value was < 0.0125,the difference was confirmed as statistically significant difference when pairwise comparison of chi-square segmentation was used.Results1.87 patients with CML-CP with imatinib treatment-resistant were divided into early switch to alternate group(n = 29),late switch to alternate group(n = 32)and non-switch to alternate group(n = 26).2.The probabilities of CCy R at 6 months was 93.1%,71% and 34.6% in early swich to alternate group,late switch to alternate group and non-switch to alternate group respectively.There were the difference between early swich to alternate group and non-switch to alternate group(p < 0.05).There were the difference between late switch to alternate group and non-switch to alternate group(P < 0.05).There were the difference between early swich to alternate group and late switch to alternate group(p < 0.05).3.The cumulative probabilities of CCy R rate at 12 months was100%,59.3% and 40% in the early swich to alternate group,late switch to alternate group and non-switch to alternate group at 12 months.There was difference between the early swich to alternate group and non-switch to alternate group(p < 0.05).There was no difference between thelate switch to alternate group and non-switch to alternate group(p>0.05).There was difference between the early swich to alternate group and late switch to alternate group(p < 0.05).4.The cumulative probabilities of MMR reached 60.7%,48.1% and 0% at 12 months respectively among three groups.There was significant difference between early swich to alternate group and non-switch to alternate group(p < 0.05).There was the difference between late switch to alternate group and non-switch to alternate group(p < 0.05),there was no difference between the early swich to alternate group and late switch to alternate group(p >0.05).5.According to non-hematological adverse reactions,there were rash(34.6%),edema(38.5%),weight gain(19.2%),bilirubinemia(19.2%),decreased serum magnesium(15.4%)and elevated elevated gama-GGT aminotransferase(11.5%)in the imatinib group.There was 1case diagnosed with rectal cancer in the treatment of imatinib.In nilotinib group,there were rash(39.3%),pruritus(37.7%),nausea and vomiting(32.8%),edema(32.8%),bilirubinemia(42.6%),elevated gama-GGT aminotransferase(32.8%).There were 3 cases of grade 3-4 adverse reactions in patients,which could all be alleviated after dose reduction therapy or drug discontinuance.6.According to hematological adverse reactions,there were anemia(38.5%),thrombocytopenia(34.6%),leukopenia(23.1%)and neutropenia(11.5%)in imtinib group.There were anemia(45.9%),thrombocytopenia(26.2%),leukopenia(19.7%)and neutropenia(8.2%)with nilotinib treatment.There were 3 cases of grade 3-4 adverse reactions with neutropeniain with nilotinib treatment.There were grade 1-2 adverse reactions in most of the patients with nilotinib treatment.The patients could recover without any treatment.7.The median of follow-up time was 50 months(7-59 months).The probabilities of overall survival rate of(OS)in all patients was 96.6%after following up for 60 months.The probabilities of OS was100%,96.9% and 92.3% respectively after following up for 60 months.There was no difference in the probabilities of overall survival(OS)between the the early swich to alternate group and non-switch to alternate group(p > 0.05).There was no difference in the probabilities of overall survival(OS)between the the late swich to alternate group and non-switch to alternate group(p > 0.05).There was no difference in the probabilities of overall survival(OS)between the the early swich to alternate group and late switch to alternate group(p > 0.05).8.There was no difference in the probabilities of progress-free survival(PFS)between the early swich to alternate group and non-switch to alternate group(p > 0.05).There was no difference in the probabilities of progress-free survival(PFS)between the late swich to alternate group and non-switch to alternate group(p >0.05).There was no difference in the probabilities of progress-free survival(PFS)between the early swich to alternate group and late switch to alternate group(p > 0.05).9.There was significant difference in the probabilities of event-free survival(EFS)between the early swich to alternate group and late switch to alternate group(p < 0.05).There was significant difference in the probabilities of event-free survival(EFS)between the late swich to alternate group and non-switch to alternate group(p < 0.05).There was significant difference in the probabilities of event-free survival(EFS)the early swich to alternate group and late switch to alternate group(p < 0.05).10.11.The probabilities of event-free survival(EFS)was 80.8% in the patients who had obtained CCy R in 6 months of treatment after following up for 60 months.the average time of occurrence of events was 47.1 months,6 months did not obtain ccyr patients no incident rate of 21.3,the average of the time of the event was 27.1 months.The median event-free survival time was 6 months.The probabilities of event-free survival was significantly higher in CCy R group(p < 0.05),and it was significantly higher in acquired group than those who in non acquired group(P < 0.05).Conclusion1.The probabilities of CCy R and MMR were used to evaluate the efficacy of nilotinib,and the probabilities of CCy R at 6 months may be related to the long-term survival.2.The probabilities of CCy R and MMR increased after treatment of nilotinib in those patients with CML-CP imtinib treatment-failure.It is significant that the patients of early swich to alternate group were benefited more.The treatment effect was improved in early transition of nilotinib treatment.3.Nilotinib was generally well tolerated.The majority of AEs were mild to moderate in severity and were usually managed by dose modification or supportive treatment.4.The EFS time were prolonged with nilotinib therapy in the patients with CML-CP with imatinib resisitance. |
PDF Full Text Request