Proposal for the selection of either nilotinib or dasatinib therapy according to the baseline BCR-ABL mutation status. The proposal is based on the current understanding from clinical studies. Less is known of the response to bosutinib from clinical studies; however, T315I and V299L have low sensitivity to bosutinib in vitro. Choice of therapy should be considered in conjunction with tolerability and disease phase.
| Mutation status . | Dasatinib . | Nilotinib . |
|---|---|---|
| *Unclear whether current TKIs may be beneficial where a minority population of T315I is present | ||
| †Clinical efficacy was demonstrated for E255K/V in CP-CML with dasatinib therapy, although the response rates were lower than for Y253H and F359V/C.46 | ||
| ‡Clinical efficacy to nilotinib was demonstrated in 5 CP patients with G250E at baseline; however, it was among the most frequent newly detectable mutations in nilotinib treated patients after imatinib failure and was detected at the time of progression.45 Further clinical studies are required to establish long-term response. | ||
| §Q252H is classed as an intermediate sensitivity mutation to dasatinib in in vitro studies, and 1 of 6 CP patients treated with dasatinib after imatinib failure achieved an MCR and CCR.46 Further clinical studies are required to establish clinical efficacy. | ||
| No mutation | Yes | Yes |
| T315I* | No | No |
| F317L/I/V | No | Yes |
| Y253H E255K/V† F359V/C | Yes | No |
| T315A | No | Yes |
| V299L | No | Yes |
| G250E | Yes | Yes‡ |
| Q252H | ?§ | Yes |
| Other mutations | Yes | Yes |
| Mutation status . | Dasatinib . | Nilotinib . |
|---|---|---|
| *Unclear whether current TKIs may be beneficial where a minority population of T315I is present | ||
| †Clinical efficacy was demonstrated for E255K/V in CP-CML with dasatinib therapy, although the response rates were lower than for Y253H and F359V/C.46 | ||
| ‡Clinical efficacy to nilotinib was demonstrated in 5 CP patients with G250E at baseline; however, it was among the most frequent newly detectable mutations in nilotinib treated patients after imatinib failure and was detected at the time of progression.45 Further clinical studies are required to establish long-term response. | ||
| §Q252H is classed as an intermediate sensitivity mutation to dasatinib in in vitro studies, and 1 of 6 CP patients treated with dasatinib after imatinib failure achieved an MCR and CCR.46 Further clinical studies are required to establish clinical efficacy. | ||
| No mutation | Yes | Yes |
| T315I* | No | No |
| F317L/I/V | No | Yes |
| Y253H E255K/V† F359V/C | Yes | No |
| T315A | No | Yes |
| V299L | No | Yes |
| G250E | Yes | Yes‡ |
| Q252H | ?§ | Yes |
| Other mutations | Yes | Yes |