Time landmarks and response criteria to TKI
| Time, mo . | Failure . | Suboptimal response . | Warnings . |
|---|---|---|---|
| Diagnosis | NA | NA | High risk; del(9q-); additional cytogenetic abnormalities in Ph+ cells |
| 3 | No HR; stable disease or disease progression | Less than CHR | NA |
| 6 | Less than CHR; no cytogenetic response: Ph+ > 95% | Less than PCyR; Ph+ > 35% | NA |
| 12 | Less than PCyR; Ph+ > 35% | Less than CCyR | Less than MMR |
| 18 | Less than CCyR | Less than MMR | NA |
| Anytime | Loss of CHR; loss of CCyR; mutation (ex. T315I) | Additional cytogenetic abnormalities in Ph+ cells; loss of MMR; mutation | Any rise in transcript level; additional cytogenetic abnormalities in Ph− cells |
| Time, mo . | Failure . | Suboptimal response . | Warnings . |
|---|---|---|---|
| Diagnosis | NA | NA | High risk; del(9q-); additional cytogenetic abnormalities in Ph+ cells |
| 3 | No HR; stable disease or disease progression | Less than CHR | NA |
| 6 | Less than CHR; no cytogenetic response: Ph+ > 95% | Less than PCyR; Ph+ > 35% | NA |
| 12 | Less than PCyR; Ph+ > 35% | Less than CCyR | Less than MMR |
| 18 | Less than CCyR | Less than MMR | NA |
| Anytime | Loss of CHR; loss of CCyR; mutation (ex. T315I) | Additional cytogenetic abnormalities in Ph+ cells; loss of MMR; mutation | Any rise in transcript level; additional cytogenetic abnormalities in Ph− cells |
These landmarks were established based on imatinib trials. For the second-generation TKI, these will probably be revised in the next year based on adult responses. Whether time to reach landmarks with the more potent second-generation TKI results in comparable clinical outcomes is not currently known. The most important landmark and predictor for success is complete cytogenetic response.
NA indicates not applicable.
Adapted from Goldman40 and Baccarani et al41 with permission.