| Objective In this study,we analyzed the clinical outcomes of patients with chronic myelogenous leukemia(CML)in the chronic phase after discontinuation of tyrosine kinase inhibitor(TKI)therapy through a prospective study and explored the clinical factors affecting the discontinuation of TKI.Methods From December 2015 to March 2020,47 CML patients in chronic phase with complete clinical data before drug withdrawal and clear clinical outcome after drug withdrawal were selected from the Department of Hematology,Shenzhen Second People’s Hospital.To observe the maintenance of molecular remission after drug withdrawal,analyze the differences in clinical characteristics between the relapsed and non-relapsed groups,calculate the treatment-free remission(TFR)rate at6 and 12 months after drug withdrawal,and explore the influencing factors of safe discontinuation of TKI therapy in CML patients.Results The included 47 patients had a TKI treatment time of 78 months(range,21 - 172 months)and a sustained molecular response time of 60 months(range,14 -126 months);4 patients achieved major molecular response(MMR),3patients achieved molecular MR 4.0,and 40 patients had negative BCR-ABL transcripts(UMRD)in peripheral blood at the time of discontinuation.After 20 months of follow-up after TKI discontinuation,22 patients(46.8%)lost their MMR,and the time to recurrence was 5.5 months(1.0-29.0 months);at 12 months,a total of 18 patients(38.3%)had molecular recurrence,of which 14 occurred in the first 6 months.The TFR rates at 6 and 12 months after discontinuation were 70.2% and 61.7%,respectively.Of the 22 patients with recurrence,20 patients resumed TKI treatment within the cut-off follow-up time,and the time to resumption of TKI treatment was3.5 months(0-7.0 months).None of them changed the type and dose of TKI.MMR or deep-seated molecular response(DMR)was regained 2.0 months(1.0-13.0months)after resumption of TKI treatment.One patient did not resume medication because the time to recurrence was similar to the cut-off follow-up time,and the other patient was lost to follow-up after recurrence.Nineteen patients achieved UMRD at 4 months(1.0-16.0 months),including 3 patients with molecular level only MMR before discontinuation and 2 patients with molecular MR4.0.We observed that 6(12.8%)patients developed TKI withdrawal syndrome,manifested as new or aggravated skin itching,pigmentation and limb spasms,joint pain,generalized muscle or bone pain,which could be relieved after symptomatic treatment,and none of them resumed TKI treatment;in addition,univariate analysis showed that factors such as age at discontinuation(P = 0.721),gender(P = 0.773),Sokal risk stratification(P = 0.747),type of TKI(P = 0.715),time required to obtain MMR(P = 0.476),and depth of molecular response(P = 0.228)had no significant effect on recurrence.TKI treatment time before discontinuation(P = 0.002)and duration of molecular response(P = 0.030)were associated with lower molecular recurrence rates(P <0.05).In terms of the reasons for discontinuation,patients in the discontinuation group had a satisfactory TKI treatment time and molecular response time before discontinuation,which were more conducive to maintaining long-term TFR than those in the planned or accidental pregnancy,TKI-related adverse reactions,and combined solid tumors(P = 0.018).Conclusion Patients with chronic myelogenous leukemia in chronic phase who have received long-term TKI therapy and achieved sustained molecular remission can choose to stop TKI therapy at the appropriate time,and regular and close follow-up is required after discontinuation to complete BCR-ABL transcript testing on time.Patients with molecular relapse can still rapidly achieve molecular remission again after resumption of TKI therapy,and even achieve a deeper molecular response.No patient had disease progression during the follow-up period. |
