Early individualization of the dosage of imatinib may optimize outcomes in patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).1
Investigators performed a randomized trial to evaluate the value of imatinib dose optimization based on the monitoring of [C]min levels in newly diagnosed patients.
A total of 133 patients diagnosed with CP-CML for less than 3 months who were either imatinib-naïve or not treated with imatinib for less than 3 months were included in the study.
Patients with a baseline [C]min < 1000 ng/mL were randomized to receive either a dose-increase strategy to reach 1000 ng/mL (arm A1; n = 43) or standard IM management (arm A2; n = 43). Those with [C]min ≥ 1000 ng/mL were included in the observational arm (A3; n = 47). The primary endpoint was major molecular response (MMR) rate at 12 months.
Results showed that patients in arm A had a significant improvement of the median IM [C]min after dose adjustment (P < .0001) when compared with arm 2. IM daily dose increased in A1 (P < .0001) and reached a mean value of 600 mg/d.
Thirteen percent of patients received 500 mg/d, 30% received 600 mg/d, and 34% received 800 mg/d. Sixteen percent of patients remained at 400 mg/d and 7% were decreased to 300 mg/d.
MMR was achieved in 63% of patients in A1 (95% CI, 49 – 77) compared with 37% in A2 (95% CI, 23- 51; P = .031). MMR rates between A1 and A3 did not differ significantly.
Adverse events occurred at similar rates in patients in arm A1 (58%) and A2 (51%). A total of 8 serious adverse events related to treatment were reported and were evenly distributed among treatment groups. Treatment discontinuation were also similar among treatment groups, however there was a trend for more treatment failures in A2 vs A1 (60% vs 18%; P = .08).
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Researchers concluded that approximately 33% of patients on IM400 were correctly dosed and may not require systemic high-dose IM. Most patients did not receive adequate IM exposure and may benefit from individualized treatment strategies.
- Rousselot P, Johnson-Ansah H, Huguet F, et al. Personalized daily doses of imatinib by therapeutic drug monitoring increase the rates of molecular responses in patients with chronic myeloid leukemia. Final results of the randomized OPTIM imatinib study [abstract]. Blood. 2015;126(23):133.