Baseline BCR-ABL mutation status and response to nilotinib
| Baseline mutation (mutation group no.) . | Number of patients . | Patients achieving response, no. (%) . | Number of patients* . | Patients achieving CHR, no. (%) . | |
|---|---|---|---|---|---|
| Major cytogenetic response . | Complete cytogenetic response . | ||||
| Any mutation | 77† | 32 (42) | 18 (23) | 62 | 38 (61) |
| No mutation | 105 | 54 (51) | 37 (35) | 58 | 48 (82) |
| M244V (1)‡ | 10 | 7 (70) | 6 (60) | 8 | 7 (87) |
| L248V (2) | 2 | 0 (0) | 0 (0) | 1 | 0 (0) |
| G250E (2) | 4 | 3 (75) | 1 (25) | 4 | 3 (75) |
| Y253F | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| Y253H (3) | 7 | 1 (14) | 0 (0) | 5 | 0 (0) |
| E255K (3) | 5 | 1 (20) | 0 (0) | 5 | 2 (40) |
| E255V (3) | 1 | 0 (0) | 0 (0) | 1 | 0 (0) |
| E274K | 1 | 0 (0) | 0 (0) | 1 | 0 (0) |
| E275K (1) | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| D276G (1) | 2 | 1 (50) | 1 (50) | 1 | 1 (100) |
| E279K | 2 | 1 (50) | 1 (50) | 2 | 2 (100) |
| F311L | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| T315I4 | 4 | 0 (0) | 0 (0) | 4 | 0 (0) |
| F317L (1) | 2 | 0 (0) | 0 (0) | 2 | 1 (50) |
| M351T (1) | 11 | 6 (54) | 3 (27) | 9 | 6 (66) |
| E355A (1) | 1 | 1 (100) | 1 (100) | 0 | NA |
| E355G (1) | 3 | 2 (67) | 1 (33) | 1 | 1 (100) |
| F359I | 2 | 0 (0) | 0 (0) | 2 | 1 (50) |
| F359V (2) | 8 | 3 (38) | 1 (13) | 7 | 3 (43) |
| L370P | 1 | 1 (100) | 1 (100) | 0 | NA |
| L387M (1) | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| M388I | 1 | 1 (100) | 0 (0) | 1 | 1 (100) |
| H396R | 5 | 3 (60) | 1 (20) | 4 | 3 (75) |
| E450K | 1 | 1 (100) | 1 (100) | 1 | NA |
| S438C | 2 | 0 (0) | 0 (0) | 2 | 2 (100) |
| E459G | 1 | 1 (100) | 1 (100) | 1 | 1 (100) |
| E459K | 2 | 0 (0) | 0 (0) | 1 | 1 (100) |
| F486S | 2 | 0 (0) | 0 (0) | 2 | 1 (50) |
| Mutation group 1, IC50 less than 100 nM§ | 30 | 16 (53) | 11 (37) | 22 | 17 (77) |
| Mutation group 2, IC50 101-200 nM | 14 | 6 (43) | 2 (14) | 12 | 6 (50) |
| Mutation group 3, IC50 201-800 nM | 13 | 2 (15) | 0 (0) | 11 | 2 (18) |
| Mutation Group 4, IC50 more than 10 000 nM | 4 | 0 (0) | 0 (0) | 4 | 0 (0) |
| Baseline mutation (mutation group no.) . | Number of patients . | Patients achieving response, no. (%) . | Number of patients* . | Patients achieving CHR, no. (%) . | |
|---|---|---|---|---|---|
| Major cytogenetic response . | Complete cytogenetic response . | ||||
| Any mutation | 77† | 32 (42) | 18 (23) | 62 | 38 (61) |
| No mutation | 105 | 54 (51) | 37 (35) | 58 | 48 (82) |
| M244V (1)‡ | 10 | 7 (70) | 6 (60) | 8 | 7 (87) |
| L248V (2) | 2 | 0 (0) | 0 (0) | 1 | 0 (0) |
| G250E (2) | 4 | 3 (75) | 1 (25) | 4 | 3 (75) |
| Y253F | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| Y253H (3) | 7 | 1 (14) | 0 (0) | 5 | 0 (0) |
| E255K (3) | 5 | 1 (20) | 0 (0) | 5 | 2 (40) |
| E255V (3) | 1 | 0 (0) | 0 (0) | 1 | 0 (0) |
| E274K | 1 | 0 (0) | 0 (0) | 1 | 0 (0) |
| E275K (1) | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| D276G (1) | 2 | 1 (50) | 1 (50) | 1 | 1 (100) |
| E279K | 2 | 1 (50) | 1 (50) | 2 | 2 (100) |
| F311L | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| T315I4 | 4 | 0 (0) | 0 (0) | 4 | 0 (0) |
| F317L (1) | 2 | 0 (0) | 0 (0) | 2 | 1 (50) |
| M351T (1) | 11 | 6 (54) | 3 (27) | 9 | 6 (66) |
| E355A (1) | 1 | 1 (100) | 1 (100) | 0 | NA |
| E355G (1) | 3 | 2 (67) | 1 (33) | 1 | 1 (100) |
| F359I | 2 | 0 (0) | 0 (0) | 2 | 1 (50) |
| F359V (2) | 8 | 3 (38) | 1 (13) | 7 | 3 (43) |
| L370P | 1 | 1 (100) | 1 (100) | 0 | NA |
| L387M (1) | 1 | 0 (0) | 0 (0) | 1 | 1 (100) |
| M388I | 1 | 1 (100) | 0 (0) | 1 | 1 (100) |
| H396R | 5 | 3 (60) | 1 (20) | 4 | 3 (75) |
| E450K | 1 | 1 (100) | 1 (100) | 1 | NA |
| S438C | 2 | 0 (0) | 0 (0) | 2 | 2 (100) |
| E459G | 1 | 1 (100) | 1 (100) | 1 | 1 (100) |
| E459K | 2 | 0 (0) | 0 (0) | 1 | 1 (100) |
| F486S | 2 | 0 (0) | 0 (0) | 2 | 1 (50) |
| Mutation group 1, IC50 less than 100 nM§ | 30 | 16 (53) | 11 (37) | 22 | 17 (77) |
| Mutation group 2, IC50 101-200 nM | 14 | 6 (43) | 2 (14) | 12 | 6 (50) |
| Mutation group 3, IC50 201-800 nM | 13 | 2 (15) | 0 (0) | 11 | 2 (18) |
| Mutation Group 4, IC50 more than 10 000 nM | 4 | 0 (0) | 0 (0) | 4 | 0 (0) |
NA indicates not applicable.
Number of patients who did not have CHR at baseline and were assessable for hematologic response.
A total of 6 (8%) of 77 patients had more than 1 mutation detected at baseline with the following genotypes: H396R/M351T, D276G/M351T, E459K/M351T, E274K/T315I, E255V/M244V/T315I, and H396R/T315I.
Number in parentheses refers to the IC50-based grouping.
Mutations were grouped based on available nilotinib IC50 data established in in vitro Ba/F3 proliferation assay:18 mutation group 1 (IC50 < 100 nM), mutation group 2 (IC50 = 101-200 nM), mutation group 3 (IC50 = 201-800 nM), and mutation group 4 (IC50 > 10 000 nM). Individual mutations in each group were notated with the group number. Mutations without group number notation do not have IC50 data described in Weisberg et al.18