Real-world efficacy and safety outcomes of imatinib treatment in
patients with chronic myeloid leukemia: an Australian experience
Abstract
Background: Tyrosine kinase inhibitors (TKI) have revolutionised the
treatment of chronic myeloid leukaemia (CML), but patients still
experience treatment-limiting toxicities or therapeutic failure. Aims:
To investigate real-world use and outcomes of imatinib in patients with
CML in Australia. Methods: A retrospective cohort study of patients with
CML commencing imatinib (2001-2018) was conducted across two sites.
Prescribing patterns, tolerability outcomes, survival and molecular
response were evaluated. Results: 86 patients received 89 imatinib
treatments. Dose modifications were frequently observed (12-month rate
of 58%). At last follow-up, 62 patients (5-year rate of 55%) had
permanently discontinued imatinib treatment, of which 44 switched to
another TKI (5-year rate of 46%). Within 3 months of starting imatinib,
43% (95% CI, 32–53%) of patients experienced imatinib-related grade
≥3 adverse drug reactions (ADRs). Higher comorbidity score, lower body
weight, higher imatinib starting dose, and Middle Eastern or North
African ancestry were associated with a higher risk of grade ≥ 3 ADR
occurrence on multivariable analysis (MVA). Estimated overall survival
and event-free survival rates at 3 years were 97% (95% CI, 92–100%)
and 81% (95% CI, 72–92%), respectively. Cumulative incidence of
major molecular response (MMR) at 3 years was 63% (95% CI, 50–73%).
On MVA, imatinib starting dose, ELTS score, BCR-ABL1 transcript type,
pre-existing pulmonary disease, and potential drug-drug interactions
were predictive of MMR. Conclusion: Imatinib induced deep molecular
responses that translated to good survival outcomes in a real-world
setting, but was associated with a higher incidence of ADRs, dose
modifications and treatment discontinuations than in clinical trials.