Predictive Value Of Early Molecular Response For Deep Molecular Response In Chronic Phase Of Chronic Myeloid Leukemia

Objective:The patients who have achieved a sustained deep molecular response?DMR?on long-term tyrosine kinase inhibitor?TKI?therapy can successfully discontinue TKI therapy.Several studies have shown that monitoring BCR-ABL^IS levels at 3 months and 6 months after TKI treatment has important predictive value for long-term efficacy such as overall survival,disease-free survival.The objective of this study was to examine the association of BCR-ABL^IS transcript level at 3-or 6-month and other potential predictors with DMR achievement in CML-CP patients receiving TKI therapy.Methods:We performed the retrospective study in 166 CML-CP patients in first hospital of Jilin University receiving imatinib or nilotinib therapy.Peripheral blood BCR-ABL quantitative results and gender,age,blood count and Sokal score were collected.When MR4.0 was used as the primary endpoint,Kaplan-Meier was used to draw the cumulative risk curve,and Log-rank test was used to compare the difference between the quantitative level of 3 and 6 months to the future MR4.0.When multiple comparisons were involved,Bonferroni correction was used to correct the test level,with a P value<0.0167 as the significant difference.BCR-ABL^ISS for 3 months and 6 months and baseline indicators such as gender,age and Sokal score at the time of initial diagnosis were used to analyze.A multivariate Cox proportional hazards regression analysis was performed by inputting the single variables for which P<0.2 to find the independent factors affecting MR 4.0.furthermore,When EMR was used as the main observation index,the difference of EMR between imatinib and nilotinib was compared according to the BCR-ABL^IS quantitative level of imatinib and nilotinib for 3 and 6 months.This difference was analyzed by Pearson's?² test or Fisher's exact test.A P value of<0.05was considered statistically significant.Results:We found that CML-CP patients who achieved MR4.0 accounted for a higher percentage in the patients who achieved early molecular response(EMR:3-month BCR-ABL^IS?10%,6-month BCR-ABL^IS<1%)than that in the patients who did not achieve EMR?P₁=0.003,P₂<0.001?using Kaplan-Meier analysis.In addition,3-month BCR-ABL^IS?1%had a greater contribution to MR4.0 achievement than 1%<3-month BCR-ABL^IS?10%and 3-month BCR-ABL^IS>10%?P₁=0.014?P₂<0.001?.Similarly,6-month BCR-ABL^IS?0.1%had a greater contribution to MR4.0 achievement than 0.1%<6-month BCR-ABL^IS<1%and 6-month BCR-ABL^IS?1%?P₁=0.001,P₂?0.001?.In a multivariate COX proportional hazards regression analysis BCR-ABL^ISS transcript level at 3and 6 months of TKI therapy was an independent factor for the achievement of MR4.0 which was nevertheless not related to age,gender,Sokal score,and white blood cell?WBC?count at the initial time of diagnosis.In addition,nilotinib therapy appeared to achieve EMR more quickly than imatinib?96.4%vs.62.3%on 3-month nilotinib therapy,P<0.001;91.7%vs 55.1%on 6-month nilotinib therapy,P=0.001?,suggesting a higher therapeutic value for CML-CP.Conclusions:1.EMR achievement correlates with DMR achievement.There is a priority for achieving MR4.0 in CML-CP patients who had 3-month BCR-ABL^IS?1%and 6-month BCR-ABL^IS?0.1%,which prompts us to reconsider a new treatment goal in 3 and 6 month for CML-CP patients seeking treatment free remission?TFR?.2.Nilotinib appears to have a higher therapeutic value for CML-CP than imatinib,even at the early stage of the treatment.