Efficacy by baseline BCR-ABL mutational analysis
| . | Total* n/N (%) . | Patients with MCyR n/N (%) . | Patients with CHR n/N (%) . | |||
|---|---|---|---|---|---|---|
| Dasatinib; N = 92 . | High-dose imatinib; N = 46 . | Dasatinib . | High-dose imatinib . | Dasatinib . | High-dose imatinib . | |
| No mutations | 51 (55) | 35 (76) | 28/51 (55) | 12/35 (34) | 50/51 (98) | 32/35 (91) |
| Any mutation | 41 (45) | 11 (24) | 19/41 (46) | 3/11 (27) | 36/41 (88) | 6/11 (55) |
| Mutation associated with ≥5-fold increase in imatinib resistance | 25 (27) | 7 (15) | 12/25 (48) | 1/7 (14) | 21/25 (84) | 2/7 (29) |
| Specific BCR-ABL point mutations† | ||||||
| L248V | 2 | 0 | 1 | NA | 2 | NA |
| I418V | 1 | 1 | 1 | 1 | 1 | 1 |
| M351T (IC50: 880 nmol/L)‡ | 6 | 1 | 2 | 0 | 6 | 1 |
| F317L (IC50: 1050 nmol/L)‡ | 4 | 0 | 1 | NA | 4 | NA |
| G250E (IC50: 1350 nmol/L)‡ | 7 | 0 | 4 | NA | 6 | NA |
| H396R (IC50: 1750 nmol/L)‡ | 3 | 0 | 1 | NA | 2 | NA |
| F359V (IC50: 1825 nmol/L)‡ | 4 | 2 | 1 | 1 | 4 | 1 |
| M244V (IC50: 2000 nmol/L)‡ | 9 | 3 | 5 | 0 | 8 | 1 |
| Y253H (IC50: >6400 nmol/L)‡ | 1 | 1 | 0 | 0 | 0 | 0 |
| T315l (IC50: >6400 nmol/L)‡ | 3 | 0 | 1 | NA | 1 | NA |
| P-loop (amino acids 248 to 256) | 10 (11) | 2 (4) | 5/10 (50) | 0/2 | 8/10 (80) | 0/2 |
| A-loop (amino acids 379 to 398) | 8 (9) | 0 | 4/8 (50) | NA | 7/8 (88) | NA |
| Other regions | 24 (26) | 9 (20) | 10/24 (42) | 3/9 (33) | 21/24 (88) | 6/9 (67) |
| . | Total* n/N (%) . | Patients with MCyR n/N (%) . | Patients with CHR n/N (%) . | |||
|---|---|---|---|---|---|---|
| Dasatinib; N = 92 . | High-dose imatinib; N = 46 . | Dasatinib . | High-dose imatinib . | Dasatinib . | High-dose imatinib . | |
| No mutations | 51 (55) | 35 (76) | 28/51 (55) | 12/35 (34) | 50/51 (98) | 32/35 (91) |
| Any mutation | 41 (45) | 11 (24) | 19/41 (46) | 3/11 (27) | 36/41 (88) | 6/11 (55) |
| Mutation associated with ≥5-fold increase in imatinib resistance | 25 (27) | 7 (15) | 12/25 (48) | 1/7 (14) | 21/25 (84) | 2/7 (29) |
| Specific BCR-ABL point mutations† | ||||||
| L248V | 2 | 0 | 1 | NA | 2 | NA |
| I418V | 1 | 1 | 1 | 1 | 1 | 1 |
| M351T (IC50: 880 nmol/L)‡ | 6 | 1 | 2 | 0 | 6 | 1 |
| F317L (IC50: 1050 nmol/L)‡ | 4 | 0 | 1 | NA | 4 | NA |
| G250E (IC50: 1350 nmol/L)‡ | 7 | 0 | 4 | NA | 6 | NA |
| H396R (IC50: 1750 nmol/L)‡ | 3 | 0 | 1 | NA | 2 | NA |
| F359V (IC50: 1825 nmol/L)‡ | 4 | 2 | 1 | 1 | 4 | 1 |
| M244V (IC50: 2000 nmol/L)‡ | 9 | 3 | 5 | 0 | 8 | 1 |
| Y253H (IC50: >6400 nmol/L)‡ | 1 | 1 | 0 | 0 | 0 | 0 |
| T315l (IC50: >6400 nmol/L)‡ | 3 | 0 | 1 | NA | 1 | NA |
| P-loop (amino acids 248 to 256) | 10 (11) | 2 (4) | 5/10 (50) | 0/2 | 8/10 (80) | 0/2 |
| A-loop (amino acids 379 to 398) | 8 (9) | 0 | 4/8 (50) | NA | 7/8 (88) | NA |
| Other regions | 24 (26) | 9 (20) | 10/24 (42) | 3/9 (33) | 21/24 (88) | 6/9 (67) |
n/N, number responding/number treated; CHR, complete hematologic response; MCyR, major cytogenetic response; NA, not applicable.
Twelve of 150 patients had no mutational analysis performed at baseline (dasatinib, 9; high-dose imatinib, 3).
Reported in 2 or more patients.
Cellular IC50 values taken from O'Hare et al, 2005.