Table 3.
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 |
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.