Table 2.
Response rates according to baseline BCR-ABL1 mutation for the 20 mutants detected by NGS in at least 2 patients
| Unique NGS baseline mutations | Patients (NGS) | Patients (SS) | Patients (LL) | IC50 (nM)* | MCyR rate (%)† | MMR rate (%)† |
|---|---|---|---|---|---|---|
| T315I | 74 | 64 | 10 | 6 | 50/74 (68) | 40/74 (54) |
| F317L | 29 | 22 | 7 | 4 | 13/29 (45) | 12/29 (41) |
| F359V | 20 | 13 | 7 | 4 | 11/20 (55) | 8/20 (40) |
| E255K | 13 | 8 | 5 | 6 | 8/13 (61.5) | 6/13 (46) |
| G250E | 12 | 8 | 4 | 5 | 8/12 (67) | 4/12 (33) |
| M244V | 9 | 5 | 4 | 3 | 4/9 (56) | 3/9 (33) |
| V299L | 8 | 5 | 3 | 4 | 3/8 (37.5) | 2/8 (25) |
| F359C | 7 | 4 | 3 | 6 | 1/7 (14) | 0/7 (0) |
| E459K | 7 | 3 | 4 | 5 | 3/7 (43) | 3/7 (43) |
| H396R | 5 | 5 | 0 | 4 | 1/5 (20)‡ | 2/5 (40) |
| E255V | 4 | 2 | 2 | 16 | 1/4 | 0/4 |
| F359I | 4 | 4 | 0 | 11 | 3/4 | 1/4 |
| L248V | 2 | 2 | 0 | 4 | 1/2 | 1/2 |
| Q252H | 2 | 1 | 1 | ND | 2/2 | 2/2 |
| Y253H | 2 | 2 | 0 | 5 | 1/2 | 1/2 |
| E279K | 2 | 1 | 1 | ND | 0/2§ | 1/2 |
| M351T | 2 | 1 | 1 | 4 | 1/2 | 1/2 |
| E355A | 2 | 2 | 0 | 7 | 1/2 | 1/2 |
| H396P | 2 | 1 | 1 | ND | 1/2 | 0/2 |
| M437I | 2 | 0 | 2 | ND | 1/2 | 1/2 |
ND, not determined.
The mutations are sorted by number of patients with the corresponding mutant as detected by NGS, and then by ascending amino acid sequence.
IC50 values are based on ponatinib potency in Ba/F3 cells harboring the corresponding BCR-ABL1 mutation.29
MCyR rate by 12 months or MMR rate at any time is reported based on patients with mutations detected by NGS in this study; percent of MCyR or MMR is shown when the number of evaluable patients was ≥5. Bold font denotes exact substitutions at amino acids previously associated with TKI resistance4; nonbolded font denotes a substitution at an amino acid not previously associated with TKI resistance.
One patient achieved MMR at 12 months but did not have documented evidence of MCyR by 12 months because CyR was not assessed between 3 and 12 months; therefore, this patient was not included as achieving MCyR.
In one patient, MMR was achieved at 9 months; however, cytogenetic response was not assessed between months 3 and 12.