Efficacy of dasatinib by baseline BCR-ABL mutational analysis of patients with imatinib-resistant or -intolerant chronic myeloid leukemia at 8 months' follow-up
| . | Total* . | Patients with CHR . | Patients with MCyR . |
|---|---|---|---|
| No imatinib-resistant mutation, no. (%) | 107 (59) | 98/107 (92) | 58/107 (54) |
| Any imatinib-resistant mutation,* no. (%) | 73 (41) | 65/73 (89) | 36/73 (49) |
| Mutation associated with at least 5-fold increase in imatinib resistance,† no. (%) | 46 (26) | 40/46 (87) | 21/46 (46) |
| Key mutations with high-level imatinib resistance,‡ no. | |||
| Q252H (IC50, 1325 nmol/L)‡ | 3 | 2 | 1 |
| G250E (IC50, 1350 nmol/L)‡ | 13 | 13 | 7 |
| H396R (IC50, 1750 nmol/L)‡ | 10 | 8 | 4 |
| F359V (IC50, 1825 nmol/L)‡ | 2 | 2 | 2 |
| M244V (IC50, 2000 nmol/L)‡ | 7 | 7 | 5 |
| E255K (IC50, 5200 nmol/L)‡ | 2 | 2 | 0 |
| Y253H (IC50, > 6400 nmol/L)‡ | 4 | 4 | 3 |
| E255V (IC50, > 6400 nmol/L)‡ | 3 | 3 | 1 |
| T315I (IC50, > 6400 nmol/L)‡ | 3 | 0 | 0 |
| P-loop (amino acids 244-255), no. (%) | 35 (29) | 34/35 (97) | 17/35 (49) |
| A-loop (amino acids 379-398), no. (%) | 16 (9) | 12/16 (75) | 7/16 (44) |
| Other regions only, no. (%) | 24 (13) | 21/24 (88) | 13/24 (54) |
| . | Total* . | Patients with CHR . | Patients with MCyR . |
|---|---|---|---|
| No imatinib-resistant mutation, no. (%) | 107 (59) | 98/107 (92) | 58/107 (54) |
| Any imatinib-resistant mutation,* no. (%) | 73 (41) | 65/73 (89) | 36/73 (49) |
| Mutation associated with at least 5-fold increase in imatinib resistance,† no. (%) | 46 (26) | 40/46 (87) | 21/46 (46) |
| Key mutations with high-level imatinib resistance,‡ no. | |||
| Q252H (IC50, 1325 nmol/L)‡ | 3 | 2 | 1 |
| G250E (IC50, 1350 nmol/L)‡ | 13 | 13 | 7 |
| H396R (IC50, 1750 nmol/L)‡ | 10 | 8 | 4 |
| F359V (IC50, 1825 nmol/L)‡ | 2 | 2 | 2 |
| M244V (IC50, 2000 nmol/L)‡ | 7 | 7 | 5 |
| E255K (IC50, 5200 nmol/L)‡ | 2 | 2 | 0 |
| Y253H (IC50, > 6400 nmol/L)‡ | 4 | 4 | 3 |
| E255V (IC50, > 6400 nmol/L)‡ | 3 | 3 | 1 |
| T315I (IC50, > 6400 nmol/L)‡ | 3 | 0 | 0 |
| P-loop (amino acids 244-255), no. (%) | 35 (29) | 34/35 (97) | 17/35 (49) |
| A-loop (amino acids 379-398), no. (%) | 16 (9) | 12/16 (75) | 7/16 (44) |
| Other regions only, no. (%) | 24 (13) | 21/24 (88) | 13/24 (54) |
CHR indicates complete hematologic response; MCyR, major cytogenetic response.
Six of 186 subjects (all from the imatinib-resistant cohort) had mutations identified at the site prior to study entry; because these mutations were not confirmed by the central laboratory, corresponding data are not included; thus, total n = 180.
At least 5-fold increase in cellular IC50 compared with unmutated BCR-ABL.
Taken from O'Hare et al.14