ORLANDO, FL—Tailoring imatinib dose adjustments based on therapeutic drug monitoring can result in higher rates of major molecular response (MMR) in patients with newly diagnosed chronic myeloid leukemia in the chronic phase (CP-CML), results of a randomized study presented at the 57th American Society of Hematology (ASH) Annual Meeting have found.1
The study showed that 36% of patients on imatinib 400 mg were correctly dosed—and therefore may not require systemic high-dose imatinib—while 64% of patients were not exposed to imatinib at the standard dose, with the potential to benefit from individualized strategies, said Philippe Rousselot, MD, PhD, of Hôpital André Mignot in France.
Patients with high imatinib trough levels are known to achieve higher rates of MMR, with a [C]min value threshold of 1000 ng/mL to predict such response.
To evaluate the value of imatinib dose optimization based on [C]min level monitoring, the OPTIM study enrolled patients with a diagnosis of CP-CML of less than 3 months and determined imatinib [C] min by chromatography–tandem mass spectrometry 15 days after enrollment. Those with a [C]min less than 1000 ng/mL were randomly assigned to a dose-increase strategy, with the goal of reaching the 1000 ng/mL threshold (arm A, 43 patients), or standard imatinib management (arm B, 43 patients). Patients with [C]min levels 1000 ng/mL or higher were observed (arm C, 47 patients).
Imatinib [C]min levels were assessed monthly in arms A and B and every 3 months in arm C. BCR-ABLIS was assessed every 3 months. Primary study end point was MMR rates at 12 months.
Median age of the patients was 64 (range, 25 to 88); the male-to-female sex ratio was 1.4; and the Sokal score was high in 21%, intermediate in 41%, and low in 38%, the latter equally distributed among the 3 arms.
A total of 12 patients (9%) discontinued treatment during the first 12 months postrandomization, 4 in arm C, 6 in arm B, and 2 in arm C.
At 12 months’ randomization, 76% of patients in arm A had an MMR, compared with 44% for arm B (P = 0.002); the rate was 56% in arm C. The estimated MMR at 12 months was 77% in arm A and 50% in arm B (P = 0.016).
A total of 203 patients reported adverse events, which were similar between arms A and C; this included musculoskeletal symptoms, gastrointestinal symptoms, blood cell counts, and skin and mucosal complaints.
Dr Rousselot concluded that therapeutic drug monitoring in the era of generic imatinib is feasible to maximize response to therapy; however, it may represent “a medico-economic challenge” for first-line treatment.
1. 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. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting; December 5, 2015, Orlando, FL.