Less frequent monitoring of BCR-ABL1 after discontinuation of a frontline tyrosine kinase inhibitor (TKI) may not affect clinical outcomes for patients with chronic myeloid leukemia (CML), according to findings published in Cancer.1
The optimal frequency of monitoring after TKI discontinuation in patients with CML remains unclear, and there are limited data on the use of second-generation TKIs in the first-line treatment setting or after failure of frontline therapy.
To evaluate the real-world experience of reduced frequency molecular monitoring among patients with CML, investigators analyzed medical record data from patients in all phases of CML who discontinued treatment with imatinib, dasatinib, or bosutinib.
Blood quantitative reverse transcriptase-polymerase chain reaction testing for BCR-ABL1 was performed monthly for 3 months, quarterly for 12 months, and every 6 months thereafter until loss of major molecular response (MMR). After patients lost MMR, the patient reinitiated the previously discontinued TKI.
During a period of about 5 years, 24 patients discontinued treatment, including 21 in chronic phase, 2 in accelerated phase, and 1 in lymphoid blast phase. Sixteen, 5, and 3 patients discontinued imatinib, dasatinib, and bosutinib used as first-line treatment or beyond, respectively.
Twenty-four patients underwent BCR-ABL1 testing 1.3 ± 0.7 times within the first 3 months; 18 patients received the test 2.7 ± 1.4 times in the following 12 months.
Median follow-up was 36.5 months. Results showed that 65.7% (95% CI, 55.8-75.6) of patients who discontinued therapy were likely to remain in treatment-free remission at 1 year; 59.7% (95% CI, 49.1-70.3) had a 2-year treatment-free remission rate. Researchers observed loss of MMR in 9 patients at a median of 2.8 months following the discontinuation of TKI therapy.
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Although this study is limited by its small sample size, the findings suggest that lower-frequency monitoring of BCR-ABL1 may not affect patient outcomes in this subpopulation. These results also support the feasibility of discontinuation of first-line treatment or beyond TKIs after resistance or intolerance to first-line therapy. Larger studies are needed to validate these findings.
- Kong JH, Winton EF, Heffner LT, et al. Does the frequency of molecular monitoring after tyrosine kinase inhibitor discontinuation affect outcomes of patients with chronic myeloid leukemia? Cancer. 2017 Feb 27. doi: 10.1002/cncr.30608 [Epub ahead of print]