Aim:To observe and assess whether TKI can be de-escalated or discontinued without occurrence of molecular relapse in CML patients,who with continuous effective TKI over 5 years and maintain MR4.5(BCR-ABLIS≤0.0032%) at least 18 months.
Methods: In this study,we conducted half standard TKI dose or discontinued treatment in patients with CML who were aged 18 years and older and duration effective TKI treatment at least 5 years,duration MR4.5 monitored by quantitative polymerase chain reaction(Q-PCR) in recent 18 months.Blood concentration and immune function were also monitored.Molecular relapse was defined as loss of MMR(BCR-ABLIS>0.1%), these patients restore the original dose at once.
Results: 44 patients were enrolled between Jan 2016,and Jun 2019,35 in de-escalation group and 9 in discontinue group.In the de-escalation group,45.7% males,median age was 48(23-75) years,valid TKI therapy duration 84(60-204) months,and median sustained MR4.5 was 25(19-160) months.Follow-up 1 year,5(14.3%) of these 35 patients occurrence of molecular relapsed(3 before 6 months,one at month 8, one at month 9),all of them showed decreases in their BCR-ABL levels after reintroduction of original TKI dose.In the discontinue arm,55.6% males,the age ranged from 28 to 56,the median effective TKI treatment was 72(60-108) months and remained of MR4.5 was 36(18-72) months.Molecular recurrence-free events were 66.7% at 12 months,3 patients relapsed events occurred in discontinuous month 1,month 6 and month 12,respectively.All of them showed great reaction when treatment was restarted.Supervised patients blood concentration between standard treatment group and half-dose group,founded half-dose group was lower than standard group(1083.61±371.80ng/ml vs. 1622.28±771.36ng/ml ,P=0.000).The immune function of the relapse and non-relapse arm was observed,in relapsed group the proportion of CD3-/CD56+ cells was declined significantly(P=0.013).
Conclusions: Treatment-free remission(TFR) has become the main therapeutic target for CML patients. With 85.7% TFR in 12 months follow-up after de-escalation TKI treatment ,our study demonstrates that de-escalated TKI would suitable for Chinese CML patients who with a sustained deep molecular response.The vivo insufficient of drug concentration and the damaged of NK cells may cause the recurrence events.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
