Main research question:
Does digital droplet PCR (ddPCR) negativity for BCR-ABL1 predict a high (60% or higher) Treatment Free Remission (TFR) success rate in patients with a short (3-6 year) Tyrosine Kinase Inhbitor (TKI) treatment duration?
A secondary research question is if three novel tests correlate with TFR success rate, which may improve the predictive power of ddPCR testing:
a. Circulating residual CD26+CD34+ leukemic cells
b. Circulating CD56+ NK cells
c. Pneumococcal vaccine response
I CML patients treated for 3-6 years with TKI and a negative ddPCR for BCR-ABL1 have a minimal TFR success rate of 60%, thus comparable to the general success rate of patients treated >6 years
II TFR success rate is higher in patients discontinuing TKI therapy who have
a. lower levels of CD26+CD34+ leukemic cells
b. higher levels of CD56+ NK cells
c. a positive pneumococcal vaccine response
Observational cohort study
Patients eligible for attempted TFR discontinuation (chronic phase CML, no previous switch in TKI for treatment failure, minimal 3 years total TKI therapy, durable deep molecular remission defined as MR 4.0 or better)
TKI cessation in CML patients treated for 3-6 years with a TKI who are ddPCR negative for BCR-ABL1
Sustained MMR (BCR-ABL <0,1% IS) at 12 months after TKI discontinuation
For main study: calculated sample size of n=148
For substudy: estimated sample size of n=60
1. Main data analysis: Non-inferiority to a level of minimally 60% of proportion of sustained TFR at 12 months in patients with TKI treatment duration <6 years and with negative ddPCR BCR-ABL1 test.
2. Exploratory correlative analysis for three predictive factors: CD26+ leukemic cells and CD56+ NK cells as continuous variables; pneumococcal vaccine response as dichotomized and categorical variable; all vs. sustained MMR at 12 months after TKI discontinuation.