Mutational status in patients who progressed to AP/BC or lost response on treatment
| Event type . | Nilotinib 300 mg twice daily (n = 282), n . | Nilotinib 400 mg twice daily (n = 281), n . | Imatinib 400 mg once daily (n = 283), n . |
|---|---|---|---|
| Progression to AP/BC on treatment* | 2 | 3 | 12 |
| Patients with mutations at time of progression | 1 | 2 | 7 |
| Type of mutation at time of progression | E459K | Y253H/T315I, E255V | M244V, Y253H, Y253H/F359I, M351T, F359I, E459K (2) |
| Patients who achieved MMR at any time | 207 | 199 | 153 |
| Patients with confirmed loss of MMR† | 9 | 11 | 14 |
| Patients with mutations at loss of MMR | 0 | 4‡ | 3§ |
| Type of mutation at loss of MMR | Y253H, Y253H/T315I, E255V, E255K | M244V, T315I, H396R/M351T | |
| Patients who achieved CCyR at any time | 245 | 238 | 218 |
| Patients with confirmed loss of CCyR|| | 2 | 3 | 5 |
| Patients with mutations at loss of CCyR | 0 | 2‡ | 3‡ |
| Type of mutation at loss of CCyR | Y253H/T315I, E255V | Y253H/F359I, M351T, E459K |
| Event type . | Nilotinib 300 mg twice daily (n = 282), n . | Nilotinib 400 mg twice daily (n = 281), n . | Imatinib 400 mg once daily (n = 283), n . |
|---|---|---|---|
| Progression to AP/BC on treatment* | 2 | 3 | 12 |
| Patients with mutations at time of progression | 1 | 2 | 7 |
| Type of mutation at time of progression | E459K | Y253H/T315I, E255V | M244V, Y253H, Y253H/F359I, M351T, F359I, E459K (2) |
| Patients who achieved MMR at any time | 207 | 199 | 153 |
| Patients with confirmed loss of MMR† | 9 | 11 | 14 |
| Patients with mutations at loss of MMR | 0 | 4‡ | 3§ |
| Type of mutation at loss of MMR | Y253H, Y253H/T315I, E255V, E255K | M244V, T315I, H396R/M351T | |
| Patients who achieved CCyR at any time | 245 | 238 | 218 |
| Patients with confirmed loss of CCyR|| | 2 | 3 | 5 |
| Patients with mutations at loss of CCyR | 0 | 2‡ | 3‡ |
| Type of mutation at loss of CCyR | Y253H/T315I, E255V | Y253H/F359I, M351T, E459K |
Progression to AP/BC or death due to CML while on core study treatment. Estimated 3-y rates of progression-free survival in ENESTnd were previously reported (99.3%, 98.7%, and 95.2% for nilotinib 300 mg twice daily, nilotinib 400 mg twice daily, and imatinib, respectively; P = .0059 and .0185 for nilotinib 300 mg twice daily and nilotinib 400 mg twice daily, respectively, vs imatinib).11
Confirmed loss of MMR was defined as BCR-ABLIS >0.1%, with a fivefold or more rise in BCR-ABL ratio from the lowest value achieved up to that time point, confirmed by a duplicate analysis of the same sample and by another PCR sample analyzed ≥4 weeks later.
Patients later progressed to AP/BC on treatment.
Patients later discontinued due to suboptimal response.
Confirmed loss of CCyR was defined as 2 cytogenetic assessments ≥4 weeks apart with Ph+ >0%, regardless of the number of metaphases analyzed.