Clinical and molecular characteristics of patients with postbaseline mutations that were not identified by NGS at baseline
| Patient ID . | Prior TKI* . | Baseline NGS (frequency) . | Postbaseline SS (frequency) . | Achieved primary end point . | Lost primary end point . | Reason for discontinuation . | Sample analysis at . | IC50 (nM)† . | Average daily dose (mg) . | Comment . |
|---|---|---|---|---|---|---|---|---|---|---|
| 248 | I D N | G250E (1%) | E255V (100%) | Y | Y | Adverse event | EOT | 16 | 13 | Low drug exposure |
| 29 | I N | None | T315I (100%) | Y | Y | Progressive disease | EOT | 6 | 43 | Possible BCR-ABL–independent resistance |
| 155 | I D | None | T315I (100%) | Y | Y | Withdrawal by subject | EOT | 6 | 44 | Possible BCR-ABL–independent resistance |
| 121 | I N | E355A (81%) | T315I (10%) | N | N/A | On study | 1 y | 6 | 6 | Low drug exposure and re-emergence of T315I |
| E355A (10%) | 7 | |||||||||
| 262 | I D N | V299L/F359V (97%) | Y253H/F359V (100%/100%) | Y | N‡ | Progressive disease | EOT | 5 | 26 | Compound mutant at EOT |
| 158 | I D N | F359V (93%) | Y253H/F359V (100%/100%) | N | N/A | Other | EOT | 5 | 34 | Compound mutant at EOT |
| M244V (4%) | ||||||||||
| 142 | B | T315I (41%) | T315I/M351T (100%/40%) | N | N/A | Other | EOT | 27 | 45 | Compound mutant at EOT |
| 167 | I D | None | T315I/F359V (100%/90%) | Y | N‡ | Adverse event | EOT | 5 | 30 | Compound mutant at EOT |
| Patient ID . | Prior TKI* . | Baseline NGS (frequency) . | Postbaseline SS (frequency) . | Achieved primary end point . | Lost primary end point . | Reason for discontinuation . | Sample analysis at . | IC50 (nM)† . | Average daily dose (mg) . | Comment . |
|---|---|---|---|---|---|---|---|---|---|---|
| 248 | I D N | G250E (1%) | E255V (100%) | Y | Y | Adverse event | EOT | 16 | 13 | Low drug exposure |
| 29 | I N | None | T315I (100%) | Y | Y | Progressive disease | EOT | 6 | 43 | Possible BCR-ABL–independent resistance |
| 155 | I D | None | T315I (100%) | Y | Y | Withdrawal by subject | EOT | 6 | 44 | Possible BCR-ABL–independent resistance |
| 121 | I N | E355A (81%) | T315I (10%) | N | N/A | On study | 1 y | 6 | 6 | Low drug exposure and re-emergence of T315I |
| E355A (10%) | 7 | |||||||||
| 262 | I D N | V299L/F359V (97%) | Y253H/F359V (100%/100%) | Y | N‡ | Progressive disease | EOT | 5 | 26 | Compound mutant at EOT |
| 158 | I D N | F359V (93%) | Y253H/F359V (100%/100%) | N | N/A | Other | EOT | 5 | 34 | Compound mutant at EOT |
| M244V (4%) | ||||||||||
| 142 | B | T315I (41%) | T315I/M351T (100%/40%) | N | N/A | Other | EOT | 27 | 45 | Compound mutant at EOT |
| 167 | I D | None | T315I/F359V (100%/90%) | Y | N‡ | Adverse event | EOT | 5 | 30 | Compound mutant at EOT |
B, bosutinib; D, dasatinib; EOT, end of treatment; I, imatinib; N, nilotinib; N/A, not applicable.
Mutations detected postbaseline that were not detected at baseline are bolded; if such mutations had been detected before baseline (in the patient’s history), they are also underlined.
The order of TKIs from left to right indicates the sequence of TKI treatment in the patient’s history (first to last).
IC50 values are based on in vitro ponatinib activity against cells harboring bolded BCR-ABL1 mutations.29
Patient achieved primary end point; however, loss of response before discontinuation was not documented.