Factors influencing early molecular response to imatinib therapy in CML

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.

Key clinical point: In patients with chronic-phase chronic myeloid leukemia (CP-CML), steady state plasma imatinib levels, MDR1 polymorphisms, and ABC transporter expression influence early molecular response (EMR)/major molecular response (MMR) to imatinib therapy, which in turn influence failure-free survival (FFS).

Major finding: Patients with low and intermediate Sokal scores showed better 2-year FFS vs. those with high Sokal score (P = .02). Patients with variant MDR1/ABCB1-C1236T had high day 29 plasma imatinib levels (P = .005), increased EMR at 3 months (P = .044), and a better 2 year FFS (P = .003) vs. those with wild type genotype. Patients with lower ABCB1 mRNA expression showed significantly higher intracellular imatinib levels (P = .029). The median plasma imatinib level on day 29 was significantly higher in patients who achieved EMR at 3 months (P = .022) and MMR at 12 months (P = .041) which essentially resulted in better 2-year FFS (P = .05).

Study details: This prospective single center observational study evaluated factors influencing EMR to imatinib and FFS in newly diagnosed CP-CML patients (n = 160).

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Rajamani BM et al. Sci Rep. 2020 Nov 26. doi: 10.1038/s41598-020-77140-9.