Responses and outcome on third-line therapy according to the baseline characteristics of the patients
| Variable . | n . | Response to third-line therapy . | |||
|---|---|---|---|---|---|
| MCyR (%) . | CCyR (%) . | OS (%) . | EFS (%) . | ||
| Age* | P = .3 | P = .5 | P = .03 | P = .7 | |
| ≤ 64 y | 13 | 52.0 | 41.0 | 60.6 | 49.9 |
| > 64 y | 13 | 42.3 | 53.8 | 24.9 | 39.8 |
| Sex | P = .9 | P = .9 | P = .9 | P = .8 | |
| Female | 12 | 44.4 | 45.3 | 45.0 | 51.3 |
| Male | 14 | 53.1 | 55.1 | 47.6 | 41.4 |
| Status at the onset of imatinib therapy | P = .3 | P = .3 | P = .4 | P = .8 | |
| Early CP | 19 | 57.1 | 64.3 | 80.0 | 53.6 |
| Late CP† | 7 | 47.8 | 52.6 | 40.4 | 43.5 |
| Sokal risk group | P = .9 | P = .6 | P = .9 | P = .8 | |
| Low + intermediate‡ | 14 | 44.9 | 38.6 | 39.0 | 33.3 |
| High | 11 | 60.7 | 49.3 | 50.0 | 56.6 |
| Best cytogenetic response on imatinib | P = .004 | P = .01 | P = .4 | P = .1 | |
| No response | 16 | 28.6 | 13.5 | 42.4 | 32.7 |
| At least MiCyR | 10 | 85.0 | 62.5 | 57.1 | 72.0 |
| Best cytogenetic response on second-line therapy | P < .001 | P < .001 | P = .03 | P = .04 | |
| No response | 14 | 16.7 | 0 | 25.6 | 23.4 |
| At least MiCyR | 12 | 83.3 | 70.0 | 88.9 | 83.3 |
| Prior history of clonal evolution | P = .1 | P = .3 | P = .9 | P = .9 | |
| No | 18 | 49.5 | 27.8 | 57.0 | 46.1 |
| Yes | 8 | 0 | 0 | 50.0 | 50.0 |
| Prior history of KD mutation | P = .9 | P = .4 | P = .2 | P = .3 | |
| No | 14 | 45.5 | 53.2 | 50.0 | 36.9 |
| Yes | 12 | 53.1 | 50.6 | 53.9 | 54.0 |
| Prior history of hematologic resistance to TKI therapy§ | P = .007 | P = .04 | P = .4 | P = .04 | |
| No | 19 | 67.8 | 63.9 | 61.9 | 64.7 |
| Yes | 7 | 0 | 0 | 44.4 | 28.6 |
| Prior history of intolerance to TKI therapy | P = .5 | P = .5 | P = .6 | P = .3 | |
| No | 9 | 52.6 | 46.6 | 50.0 | 40.0 |
| Yes | 17 | 59.7 | 52.9 | 46.5 | 45.4 |
| Percentage of Philadelphia chromosome–positive at start of third-line therapy | P = .04 | P = .03 | P = .1 | P = .2 | |
| ≥ 95% | 22 | 48.5 | 39.1 | 50.9 | 55.9 |
| < 95% | 4 | 100 | 100 | 100 | 100 |
| Time from diagnosis to third-line therapy¶ | P = .9 | P = .7 | P = .9 | P = .9 | |
| ≤ 63 months | 11 | 46.7 | 66.7 | 45.0 | 47.0 |
| > 63 months | 12 | 50.7 | 53.5 | 51.6 | 49.0 |
| Variable . | n . | Response to third-line therapy . | |||
|---|---|---|---|---|---|
| MCyR (%) . | CCyR (%) . | OS (%) . | EFS (%) . | ||
| Age* | P = .3 | P = .5 | P = .03 | P = .7 | |
| ≤ 64 y | 13 | 52.0 | 41.0 | 60.6 | 49.9 |
| > 64 y | 13 | 42.3 | 53.8 | 24.9 | 39.8 |
| Sex | P = .9 | P = .9 | P = .9 | P = .8 | |
| Female | 12 | 44.4 | 45.3 | 45.0 | 51.3 |
| Male | 14 | 53.1 | 55.1 | 47.6 | 41.4 |
| Status at the onset of imatinib therapy | P = .3 | P = .3 | P = .4 | P = .8 | |
| Early CP | 19 | 57.1 | 64.3 | 80.0 | 53.6 |
| Late CP† | 7 | 47.8 | 52.6 | 40.4 | 43.5 |
| Sokal risk group | P = .9 | P = .6 | P = .9 | P = .8 | |
| Low + intermediate‡ | 14 | 44.9 | 38.6 | 39.0 | 33.3 |
| High | 11 | 60.7 | 49.3 | 50.0 | 56.6 |
| Best cytogenetic response on imatinib | P = .004 | P = .01 | P = .4 | P = .1 | |
| No response | 16 | 28.6 | 13.5 | 42.4 | 32.7 |
| At least MiCyR | 10 | 85.0 | 62.5 | 57.1 | 72.0 |
| Best cytogenetic response on second-line therapy | P < .001 | P < .001 | P = .03 | P = .04 | |
| No response | 14 | 16.7 | 0 | 25.6 | 23.4 |
| At least MiCyR | 12 | 83.3 | 70.0 | 88.9 | 83.3 |
| Prior history of clonal evolution | P = .1 | P = .3 | P = .9 | P = .9 | |
| No | 18 | 49.5 | 27.8 | 57.0 | 46.1 |
| Yes | 8 | 0 | 0 | 50.0 | 50.0 |
| Prior history of KD mutation | P = .9 | P = .4 | P = .2 | P = .3 | |
| No | 14 | 45.5 | 53.2 | 50.0 | 36.9 |
| Yes | 12 | 53.1 | 50.6 | 53.9 | 54.0 |
| Prior history of hematologic resistance to TKI therapy§ | P = .007 | P = .04 | P = .4 | P = .04 | |
| No | 19 | 67.8 | 63.9 | 61.9 | 64.7 |
| Yes | 7 | 0 | 0 | 44.4 | 28.6 |
| Prior history of intolerance to TKI therapy | P = .5 | P = .5 | P = .6 | P = .3 | |
| No | 9 | 52.6 | 46.6 | 50.0 | 40.0 |
| Yes | 17 | 59.7 | 52.9 | 46.5 | 45.4 |
| Percentage of Philadelphia chromosome–positive at start of third-line therapy | P = .04 | P = .03 | P = .1 | P = .2 | |
| ≥ 95% | 22 | 48.5 | 39.1 | 50.9 | 55.9 |
| < 95% | 4 | 100 | 100 | 100 | 100 |
| Time from diagnosis to third-line therapy¶ | P = .9 | P = .7 | P = .9 | P = .9 | |
| ≤ 63 months | 11 | 46.7 | 66.7 | 45.0 | 47.0 |
| > 63 months | 12 | 50.7 | 53.5 | 51.6 | 49.0 |
The table shows the characteristics of the patients at the moment of starting third-line therapy and the 30-month probabilities of MCyR, CCyR, OS and EFS.
Median age at the onset of third-line therapy was 64 years.
Patients were considered to be in late CP at the moment of starting imatinib if they had commenced the imatinib > 6 months after diagnosis or had received prior interferon-α therapy.
One patient was classified as low risk and 13 as intermediate risk. The Sokal score could not be calculated in one patient.
Hematologic resistance was defined as either failure to achieve a CHR or loss of a previously achieved CHR.
Sixty-three months was the median time from diagnosis of CML to the start of third-line therapy.