Final Results of the OPTIM Imatinib Study in Patients with CML: Personalized Daily Doses of Imatinib by Therapeutic Drug Monitoring
Imatinib mesylate (IM) at 400 mg/day is the standard of care as first-line therapy in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CP-CML). Based on evidence that patients with high imatinib trough levels achieved higher rates of major molecular response (MMR), the randomized OPTIM imatinib trial was conducted to evaluate the value of imatinib dose optimization according to imatinib Cmin levels in newly diagnosed patients with CP-CML.1,2
Based on imatinib Cmin levels as determined by chromatography–tandem mass–mass spectrometry 15 days after enrollment, patients with a Cmin level <1000 ng/mL were randomized to 2 arms: a dose-increase strategy with dose adjustment every 4 weeks aiming to reach the threshold of 1000 ng/mL (arm A1) versus standard IM management (arm A2); patients with imatinib Cmin levels ?1000 ng/mL were observed on imatinib 400 mg/day (arm A3). Of the 133 evaluable patients, 64% showed initial Cmin <1000 ng/mL and were randomized between arm A1 (n = 43) and arm A2 (n = 43), while the 47 remaining patients with Cmin ?1000 ng/mL were observed in arm A3. Overall, 36% of patients are well-dosed with imatinib 400 mg/day with Cmin ?1000 ng/mL. Following dose adjustment in arm A1, there was a significant improvement in median imatinib Cmin compared with standard management in arm A2 (P <.0001). In arm A1, the imatinib daily dose increased to reach a mean value of 600 mg/day, indicating that the majority of patients were not exposed enough to imatinib at standard dose. The rates of adverse events were similar between arm A1 (58%) and arm A2 (51%). Treatment discontinuations were also comparable among the 3 arms, reaching 34.1% by 24 months. At 12 months, a higher proportion of patients in arm A1 achieved the primary end point of MMR (76% vs 44%; P = .002) compared with arm A2; however, the MMR rate was numerically lower in arm A2 compared with the standard arm A3 (44% vs 56%). Based on these results, the authors concluded that individualized dose-adjustment strategies based on pharmacology may be required to optimize the outcome for each patient.
- Larson RA, et al. Blood. 2008;111:4022-4028.
- Rousselot P, et al. ASH 2015. Abstract 133.