| Objective To observe the clinical efficacy of switching to the second generation tyrosine kinase inhibitor(TKI)(nilotinib or dasatinib) for chronic myeloid leukemia in chronic phase(CML-CP) patients who received imatinib as first-line therapy but without optimal response(include warning and failure). Methods We analyzed 125 CML-CP patients with suboptimal response(include warning and failure) to imatinib as a first-line therapy according to the Guidelines for the diagnosis and treatment of CML in China(2013 Edition). According to the time from imatinib therapy start until suboptimal response that occur during study treatment, the patients were divided into three groups. 45 patients achieved suboptimal response ≤6 months, 25 of whom continued imatinib therapy and 20 patients switched to second generation TKI therapy. 33 patients were evaluated as suboptimal response >6 months and ≤12 months, 24 of whom continued imatinib therapy and 9 patients switched to second generation TKI therapy. 47 patients got suboptimal response >12 months, 35 of them continued imatinib therapy and other 12 patients switched to second generation TKI therapy. Patients with suboptimal response switched to a second generation TKI were defined as “switchers”,and those who continued imatinib therapy were defined as “non-switchers”. Patients were stratified according to Sokal score, 54 of them in low risk group, 46 patients in intermediate risk group, and other 25 patients in high risk group. Comparisons of ratio achieving MMR and MR4.0 between switchers and non-switchers were made. And the ratio of MMR between different Sokal score group、gender and age were also compared. Cumulative probability of achieving EFS rate between switchers and non-switchers were all estimated according to Kaplan–Meier method, and the comparisons were made by the log-rank test.84 patients were non-switchers. Overall, ratio of patients with MMR is higher in switchers compared to the non-switchers(68.3% vs 45.2%), this difference is statistically significant(p=0.015); the ratio of patients with MR4.0 is also higher in switchers compared to the non-switchers(43.9% vs 27.4%, p=0.065). For the patients who had suboptimal response ≤6 months, the ratio of patients with MMR is higher in switchers compared to the non-switchers(65.0% vs 40.0%, p=0.095); the ratio of patients with MR4.0 is also higher in switchers compared to the non-switchers(40.0% vs 8.0%, p=0.010). For the patients with suboptimal response >6 months and ≤12 months, the ratio of patients with MMR is higher in switchers compared to the non-switchers(77.8% vs 37.5%, p=0.057); the ratio of patients with MR4.0 in switchers and non-switchers are 44.4% and 29.2%(p=0.438). For the patients who achieved suboptimal response >12 months, the ratio of patients with MMR in switchers and non-switchers are 58.3% and 54.3%(p=0.808); the ratio of patients with MR4.0 is 41.7% vs 40.0% in switchers and non-switchers, respectively(p=1.000). The ratio of patients with MMR is higher in sokal low risk group compared to in sokal intermediate and high risk groups(64.8% vs 43.7%, p=0.019). And in sokal intermediate and high risk group, the ratio of patients with MMR is higher in switchers compared to the non-switchers(61.9% vs 36.0%, p=0.041). In sokal low risk group, although the ratio of patients with MMR is higher in switchers compared to non-switchers(75.0% vs 55.9%), this difference is not statistically significant(p=0.132). In the man group and female group, the ratio of patients with MMR are 58.8% vs 40.0%, respectively(p=0.049). For the patients who aged more than 30 years, the ratio with MMR is 51.5%, and these aged less than 30 years is 46.4%(P=0.633). The estimated 1-year EFS rate、2-year EFS rate、3-year EFS rate and 4-year EFS rate of all switchers were higher than that of all non-switchers(82.7%、71.5%、63.6%、52.0% vs 71.4%、50.8%、40.2%、37.1%, P=0.013). Results Among the 125 patients evaluated, a total of 41 patients were switchers,Conclusion 1.CML-CP patients with suboptimal response to imatinib therapy switching to the second generation TKI was associated with higher MMR compared with continuing imatinib therapy; furthermore, for the patients with suboptimal ≤ 12 months, switchers achieved higher MMR compared with non-switchers; 2.The patients in sokal low risk group achieved higher MMR compared to in intermediate and high risk groups. Additionally, for the patients who had suboptimal response in sokal intermediate and high risk groups, switching to the second generation TKI was associated with higher MMR compared with continuing imatinib therapy; 3.CML-CP patients with suboptimal response to imatinib therapy switching to the second generation TKI achieve higher EFS rate compared with continuing imatinib therapy. |
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