A lower dosage of imatinib is sufficient to maintain undetectable disease in patients with chronic myeloid leukemia with long-term low-grade toxicity of the treatment

Abstract

The information about chronic myeloid leukemia (CML) patients with a deep molecular response of ≥ 4.5 log reduction (MR) in whom the dose of imatinib (IM) had to be reduced to relieve toxicity is insufficient. In 205 CML patients the dose of IM was reduced in 19 (31.2%) out of 61 patients with MR. The patients (12 pretreated with interferon-alpha) achieved MR after an average of 27.7 months. The duration of MR before the reduction of the dose was 16-123 (mean = 56.7) months. After the IM reduction (200 mg daily to 400 mg twice weekly for 15-90 (mean = 48) months) MR or major molecular response (MMR) was maintained in 14 (73.7%) and 2 (10.5%) patients, respectively. Three patients who lost MMR (15.8%) after the discontinuation of IM regained MR after the reintroduction of a lower dose. A lower dosage of IM should be tested for the management of side effects in patients with MR in prospective studies.

Tyrosine Kinase Inhibitor Therapy Discontinuation for Patients with Chronic Myeloid Leukaemia in Clinical Practice

“…However, it is plausible that some patients who fail to successfully stop their TKI might nevertheless remain in good remission on lower doses, which might ameliorate TKI-related adverse events and help with the burden of drug costs. Reduction of therapy appears safe [30], and mathematical modelling of clinical trial data predicts that after an initial phase of disease bulk reduction, reduced TKI doses are likely to control disease as effectively as standard doses [31]. The British De-Escalation and Stopping Treatment of Imatinib, Nilotinib or sprYcel (DESTINY) study differs from the other studies summarized in Table 1 in that patients first receive 12 months of their TKI at half the standard dose (imatinib 200 mg daily, nilotinib 200 mg twice daily or dasatinib 50 mg daily) before outright stopping.…”

Renal tuberculosis in an imatinib-treated chronic myeloid leukemia

“…This could be one of the reasons behind his susceptibility to TB infection and anergy to Mantoux test. Reduction in the maintenance dosage of imatinib is also a viable option in those who achieve good response in the early phase of the treatment 12,13 . This strategy might help negate some of the overt side effects of the drug.…”

A lower dosage of imatinib in patients with gastrointestinal stromal tumors with toxicity of the treatment

“…The gradual decrease reduced the size of the metastatic GIST and notably mitigated the adverse events. [15] Meanwhile, Faber et al [16] reported that lower dose IM can be effective in patients with chronic myeloid leukemia. Considering the high inter-individual pharmacokinetic variability of IM, these results suggest that a more individualized treatment is more appropriate than methods with fixed dosage of IM.…”