Table A2.
BCR-ABL1 Mutations at the Time of Discontinuation
| Mutation | Dasatinib 100 mg Once Daily (n = 258) | Imatinib 400 mg Once Daily (n = 258) | ||||
|---|---|---|---|---|---|---|
| Progression (n = 18) | Treatment Failure (n = 10) | Other* (n = 219) | Progression (n = 23) | Treatment Failure (n = 14) | Other† (n = 221) | |
| Mutation analysis attempted, No. (%) | 18 (100) | 9 (90) | 173 (79) | 21 (91) | 13 (93) | 180 (81) |
| No. of patients with mutation(s)‡ | 10 | 3 | 2 | 10 | 4 | 5 |
| Specific mutations, No. | ||||||
| M244V | 0 | 0 | 0 | 1 | 0 | 1 |
| L248V | 0 | 0 | 0 | 0 | 1 | 0 |
| Y253H | 0 | 0 | 0 | 0 | 1 | 0 |
| V299L | 2 | 2 | 1 | 0 | 0 | 0 |
| G250E | 0 | 0 | 0 | 0 | 1 | 2 |
| E255K/V | 0 | 0 | 0 | 1 | 1 | 0 |
| D276G | 0 | 0 | 0 | 2 | 0 | 0 |
| T315I | 6 | 1 | 1 | 0 | 0 | 0 |
| F317I/L | 3 | 0 | 1 | 0 | 0 | 2 |
| E355G | 0 | 0 | 0 | 1 | 1 | 0 |
| L359C/I/V | 0 | 0 | 0 | 4 | 0 | 0 |
| L387M | 0 | 0 | 0 | 1 | 0 | 0 |
| H396P/R | 0 | 0 | 0 | 1 | 0 | 1 |
| E450G | 0 | 0 | 0 | 0 | 1 | 0 |
| No mutation, No. | 8 | 5 | 24 | 11 | 8 | 37 |
| No amplification,§ No. | 0 | 1 | 147 | 0 | 1 | 138 |
Includes study closure (n = 147); adverse event related to study drug (n = 42); adverse event unrelated to study drug (n = 12); withdrawal of consent and patient request (n = 4 each); insufficient molecular response (n = 3); pregnancy (n = 2); and poor compliance/noncompliance, lost to follow-up, loss of complete cytogenetic response, increased BCR-ABL1, and relocation to the United States (n = 1 each).
Includes study closure (n = 162); adverse event related to study drug (n = 17); patient request (n = 10); poor compliance/noncompliance (n = 7); adverse event unrelated to study drug and no molecular response/loss of molecular response (n = 4 each); withdrawal of consent and suboptimal response (n = 3 each); lost to follow-up, insufficient cytogenetic response, and investigator request (n = 2 each); and pregnancy, recurrence of blasts in bone marrow, no complete molecular response, no major molecular response, and appearance of mutation (n = 1 each).
Mutations identified in dasatinib-treated patients were T315I (n = 8), V299L (n = 5), and F317I/L (n = 3). Mutations identified in imatinib-treated patients were F359C/I/V (n = 4); G250E (n = 3); M244V, E255K/V, D276G, F317L, E355G, and H396P/R (n = 2 each); and L248V, Y253H, L387M, and E450G (n = 1 each).
Insufficient BCR-ABL1 cDNA to assess mutations as a result of ongoing response.