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Tyrosine Kinase Inhibitor Discontinuation Safe in Patients With Chronic Myeloid Leukemia
The discontinuation of treatment with tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) reduced adverse effects and was associated with improved patient-reported outcomes, according to findings published in JAMA Oncology.
Researchers conducted a nonrandomized clinical trial involving 172 adult patients from 14 US academic medical centers, with a minimum of 3 years follow-up. Participants’ CML was well controlled with imatinib, dasatinib, nilotinib, or bosutinib.
Eighty-nine patients were women (51.7%) and the median age among participants was 60 years. Researchers discontinued TKI treatment and measured molecular recurrence, “defined as loss of major molecular response (BCR-ABL1 International Scale ratio >0.1%) by central laboratory testing,” and patient-reported outcomes.
Findings showed that 112 participants stayed in major molecular response and 104 participants achieved treatment-free remission.
Patients in treatment-free remission at 12 months reported meaningful improvements in fatigue (80.4%), depression (34.8%), diarrhea (87.5%), sleep disturbance (21.4%), and pain interference (4.5%). Patient-reported outcomes worsened when TKIs were restarted.
Key findings about molecular recurrence were as follows:
- Undetectable BCR-ABL1 at the time of TKI discontinuation (hazard ratio, 3.60; 95% CI, 1.99-6.50; P<.001) and 3 months (hazard ratio, 5.86; 95% CI, 3.07-11.1; P<.001) was independently associated with molecular recurrence.
- Molecular recurrence for patients with detectable BCR-ABL1 by standard real-time quantitative polymerase chain reaction (RQ-PCR) was 50.0% (14 of 28);
- undetectable BCR-ABL1 by RQ-PCR but detectable by droplet digital polymerase chain reaction (ddPCR) was 64.3% (36 of 56); and
- undetectable BCR-ABL1 by both ddPCR and RQ-PCR was 10.3% (9 of 87) (P≤.001).
Authors noted that additional research should be conducted to confirm the association between detectable BCR-ABL1 at time of discontinuation and higher risk of molecular recurrence.
“Our results provide important new information to inform the discussion between patients with CML and clinicians about the risks and benefits of TKI discontinuation and the potential to assess TKI cessation more accurately,” researchers concluded.
Reference:
Atallah E, Schiffer CA, Radich JP. Assessment of outcomes after stopping tyrosine kinase inhibitors among patients with chronic myeloid leukemia. JAMA Oncol. 2021;7(1):42-50. doi:10.1001/jamaoncol.2020.5774