Higher neutrophil counts are associated with successful tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia

ABSTRACT

Objective

Treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation at the first attempt is a therapeutic goal for patients with chronic phase chronic myeloid leukemia (CML-CP). However, it remains unclear whether discontinuation of TKIs at a second or subsequent attempt can be performed safely.

Patients and method

Here, we report a 72-year-old man diagnosed with CML-CP. He achieved TFR successfully after TKI discontinuation at the third attempt. Before discontinuation, the patient received imatinib, nilotinib, and finally nilotinib. His neutrophil count at the third attempt was higher than after the second attempt. We also performed a retrospective investigation of 53 patients who discontinued TKIs on the first or subsequent attempts.

Results

Overall, 64 TKI discontinuations were documented (first, 53; second, ten; third, one). We found that a higher neutrophil count at the time of TKI discontinuation (>2439/μL; hazard ratio, 0.325; 95% confidence interval, 0.137–0.772; p = 0.011) was associated independently with lower rates of molecular relapse.

Conclusion

We report a case of a patient who successfully achieved third attempt TKI discontinuation and, an increased neutrophil percentage may reflect stronger antitumor immune responses in patients with CML-CP.

KEYWORDS:

• Chronic myeloid leukemia
• ABL1 tyrosine kinase inhibitor
• tyrosine kinase inhibitor discontinuation
• third attempt tyrosine kinase inhibitor discontinuation
• higher neutrophil counts

Acknowledgements

HU, KK and SK designed study concept, done data collection and data analysis and wrote the manuscript. The other authors contributed to patient’s care. All authors approved the final version.

Disclosure statement

S.K. has received honoraria from Bristol-Myers Squibb, Novartis, Pfizer, and Otsuka Pharmaceuticals, and research funding from Bristol-Myers Squibb, Pfizer, Otsuka Pharmaceuticals, and Ohara Pharmaceuticals. The other authors declare no conflicts of interest.

Additional information

Funding

This work was supported by Grants-in-Aid for Scientific Research from the Shinnihon Foundation of Advanced Medical Treatment Research (to H.U.), the Japan Society for the Promotion of Science (21K16245 to H.U.), the Medical Research Encouragement Prize of the Japan Medical Association (to H.U.), and a Medical Research Grant from Takeda Science Foundation (to H.U.).