Impact of stopping tyrosine kinase inhibitor therapy on the molecular workload for BCR-ABL1 monitoring: a single center experience. 

Sylvie D’Haese1, Helena Claerhout1, Timothy Devos2, Gregor Verhoef2, Nancy Boeckx1

1 Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
2 Department of Hematology, University Hospitals Leuven, Leuven, Belgium

INTRODUCTION:  Discontinuation of  tyrosine kinase inhibitors (TKI) is feasible in selected CML patients, but requires close PCR monitoring of BCR-ABL1 levels. The Belgian Hematological Society proposed monthly testing the first year and bimonthly the second year after stopping TKI. We investigated the impact of this on the molecular workload, comparing it with a 3-monthly monitoring in case of TKI continuation.

METHODS: The UZ Leuven CML database includes 152 adult patients. Forty-one were eligible for TKI stop based on low Sokal score, typical BCR-ABL1 transcript, chronic phase only, >8 years on TKI and MR ≥4.5 for >2 years. While 12/41 continued TKI, 29 patients stopped. Duration of TKI stop, outcome and impact on PCR analysis within the first 24 months of stop were analyzed. 

RESULTS: In 18/29 TKI discontinuation was successful. Follow-up time ranged from 8-58 months. Thirteen patients were monitored ≤24 months, resulting in 120 PCR analysis. In 5 patients with long follow-up (>24 months), 47 PCRs were done the first 2 years of TKI stop, although based on stop-recommendations, 90 PCRs were advised. Without TKI stop in these 18 patients, there would have been 86 PCRs.

In 11/29 patients TKI withdrawal failed: relapse occurred at a median follow-up of 74 days (range 28-132 days). During this treatment-free period, 35 PCRs were performed. In case no TKI discontinuation was tried, only 4 PCRs were needed.

Taking non-relapsed and relapsed patients together, TKI stop resulted in a total of 202 PCRs during the first 24 months. If all these patients would have continued their TKI therapy, only 90 PCRs should have been done for monitoring. 

CONCLUSION: Discontinuation of TKI is feasible, but has impact on the molecular workload. In our study population, a 2.2-fold increase in PCRs was seen, however, in case of failure, this resulted in a 8.7 fold increase.