Baseline and end-of-study characteristics
| . | CP-CML, n = 270 . | AP-CML, n = 85 . | BP-CML, n = 62 . | Ph+ ALL, n = 32 . | Total,* N = 449 . |
|---|---|---|---|---|---|
| Characteristic at baseline | |||||
| Median age (range), y | 60 (18-94) | 60 (23-82) | 53 (18-74) | 62 (20-80) | 59 (18-94) |
| Female, n (%) | 126 (47) | 48 (56) | 25 (40) | 12 (38) | 211 (47) |
| Previous use of approved TKIs, n (%)† | |||||
| ≥2 drugs | 251 (93) | 80 (94) | 60 (97) | 26 (81) | 417 (93) |
| ≥3 drugs | 154 (57) | 47 (55) | 37 (60) | 12 (38) | 250 (56) |
| Median duration of previous treatment with approved TKIs (range), y† | 5.4 (0.4-13.3) | 5.1 (0.3-12.1) | 2.0 (0.1-11.6) | 1.2 (0.1-8.2) | 4.6 (0.1-13.3) |
| Resistant or intolerant to dasatinib or nilotinib, n (%) | |||||
| Resistant | 215 (80) | 74 (87) | 59 (95) | 27 (84) | 375 (84) |
| Intolerant only | 39 (14) | 6 (7) | 2 (3) | 2 (6) | 49 (11) |
| Both resistant and intolerant | 52 (19) | 11 (13) | 13 (21) | 5 (16) | 81 (18) |
| Mutation status, n (%)‡ | |||||
| No mutation detected | 138 (51) | 40 (47) | 17 (27) | 3 (9) | 198 (44) |
| BCR-ABL1T315I | 64 (24) | 18 (21) | 24 (39) | 22 (69) | 128 (29) |
| Best response to most recent regimen containing dasatinib or nilotinib, n (%)§ | |||||
| MaHR or better‖ | ND | 17 (21) | 9 (15) | 13 (43) | ND |
| MCyR or better¶ | 66 (26) | 12 (15) | 7 (11) | 8 (27) | ND |
| MMR | 8 (3) | 2 (3) | 1 (2) | 5 (17) | ND |
| Patient disposition at end of study | |||||
| Median duration of treatment, mo (range) | 32.1 (0.1-73.0) | 19.4 (0.5-71.3) | 2.9 (0.03-59.1) | 2.7 (0.1-39.3) | 16.7 (0.03-73.0) |
| Median follow-up, mo (range) | 56.8 (0.1-73.1) | 32.3 (3.6-71.8) | 6.2 (0.1-66.4) | 5.4 (0.1-59.6) | 37.3 (0.1-73.1) |
| Median dose intensity, mg/d (range) | 27.2 (5-45) | 33.1 (6-45) | ND | 0 | ND |
| Primary reason for discontinuation, n (%) | |||||
| Disease progression | 29 (11) | 26 (31) | 32 (52) | 18 (56) | 105 (23) |
| Adverse event | 57 (21) | 10 (12) | 9 (15) | 3 (9) | 79 (18) |
| Patient request | 31 (11) | 7 (8) | 3 (5) | 1 (3) | 42 (9) |
| Lack of efficacy | 15 (6) | 6 (7) | 1 (2) | 4 (13) | 26 (6) |
| Death# | 9 (3) | 5 (6) | 7 (11) | 5 (16) | 26 (6) |
| Investigator decision | 11 (4) | 5 (6) | 1 (2) | 0 | 17 (4) |
| Lost to follow-up | 0 | 3 (4) | 0 | 0 | 3 (<1) |
| Noncompliance | 3 (1) | 1 (1) | 0 | 0 | 4 (<1) |
| Protocol violation | 2 (<1) | 0 | 0 | 0 | 2 (<1) |
| Study closure** | 90 (33) | 14 (16) | 3 (5) | 0 | 107 (24) |
| Other**,†† | 14 (5) | 7 (8) | 6 (10) | 1 (3) | 28 (6) |
| . | CP-CML, n = 270 . | AP-CML, n = 85 . | BP-CML, n = 62 . | Ph+ ALL, n = 32 . | Total,* N = 449 . |
|---|---|---|---|---|---|
| Characteristic at baseline | |||||
| Median age (range), y | 60 (18-94) | 60 (23-82) | 53 (18-74) | 62 (20-80) | 59 (18-94) |
| Female, n (%) | 126 (47) | 48 (56) | 25 (40) | 12 (38) | 211 (47) |
| Previous use of approved TKIs, n (%)† | |||||
| ≥2 drugs | 251 (93) | 80 (94) | 60 (97) | 26 (81) | 417 (93) |
| ≥3 drugs | 154 (57) | 47 (55) | 37 (60) | 12 (38) | 250 (56) |
| Median duration of previous treatment with approved TKIs (range), y† | 5.4 (0.4-13.3) | 5.1 (0.3-12.1) | 2.0 (0.1-11.6) | 1.2 (0.1-8.2) | 4.6 (0.1-13.3) |
| Resistant or intolerant to dasatinib or nilotinib, n (%) | |||||
| Resistant | 215 (80) | 74 (87) | 59 (95) | 27 (84) | 375 (84) |
| Intolerant only | 39 (14) | 6 (7) | 2 (3) | 2 (6) | 49 (11) |
| Both resistant and intolerant | 52 (19) | 11 (13) | 13 (21) | 5 (16) | 81 (18) |
| Mutation status, n (%)‡ | |||||
| No mutation detected | 138 (51) | 40 (47) | 17 (27) | 3 (9) | 198 (44) |
| BCR-ABL1T315I | 64 (24) | 18 (21) | 24 (39) | 22 (69) | 128 (29) |
| Best response to most recent regimen containing dasatinib or nilotinib, n (%)§ | |||||
| MaHR or better‖ | ND | 17 (21) | 9 (15) | 13 (43) | ND |
| MCyR or better¶ | 66 (26) | 12 (15) | 7 (11) | 8 (27) | ND |
| MMR | 8 (3) | 2 (3) | 1 (2) | 5 (17) | ND |
| Patient disposition at end of study | |||||
| Median duration of treatment, mo (range) | 32.1 (0.1-73.0) | 19.4 (0.5-71.3) | 2.9 (0.03-59.1) | 2.7 (0.1-39.3) | 16.7 (0.03-73.0) |
| Median follow-up, mo (range) | 56.8 (0.1-73.1) | 32.3 (3.6-71.8) | 6.2 (0.1-66.4) | 5.4 (0.1-59.6) | 37.3 (0.1-73.1) |
| Median dose intensity, mg/d (range) | 27.2 (5-45) | 33.1 (6-45) | ND | 0 | ND |
| Primary reason for discontinuation, n (%) | |||||
| Disease progression | 29 (11) | 26 (31) | 32 (52) | 18 (56) | 105 (23) |
| Adverse event | 57 (21) | 10 (12) | 9 (15) | 3 (9) | 79 (18) |
| Patient request | 31 (11) | 7 (8) | 3 (5) | 1 (3) | 42 (9) |
| Lack of efficacy | 15 (6) | 6 (7) | 1 (2) | 4 (13) | 26 (6) |
| Death# | 9 (3) | 5 (6) | 7 (11) | 5 (16) | 26 (6) |
| Investigator decision | 11 (4) | 5 (6) | 1 (2) | 0 | 17 (4) |
| Lost to follow-up | 0 | 3 (4) | 0 | 0 | 3 (<1) |
| Noncompliance | 3 (1) | 1 (1) | 0 | 0 | 4 (<1) |
| Protocol violation | 2 (<1) | 0 | 0 | 0 | 2 (<1) |
| Study closure** | 90 (33) | 14 (16) | 3 (5) | 0 | 107 (24) |
| Other**,†† | 14 (5) | 7 (8) | 6 (10) | 1 (3) | 28 (6) |
ALL, acute lymphoblastic leukemia; AP, accelerated phase; BP, blast phase; CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; CP, chronic phase; MaHR, major hematologic response; MCyR, major cytogenetic response; MMR, major molecular response; ND, not determined; PCyR, partial cytogenetic response; Ph, Philadelphia chromosome; TKI, tyrosine kinase inhibitor.
Includes 5 patients (3 CP-CML, 2 AP-CML) who were not assigned to a cohort (postimatinib, non-T315I at baseline) but were treated.
Approved TKIs were imatinib, nilotinib, dasatinib, and bosutinib. Previous investigational TKIs received by at least 1% of patients included radotinib (received by 2% of patients), bafetinib (2%), rebastinib (2%), and XL-228 (2%).
Assessed by conventional Sanger sequencing at baseline.
Percentages were calculated according to the number of patients who received previous dasatinib or nilotinib: 256 patients with CP-CML, 80 patients with AP-CML, 61 patients with BP-CML, and 30 patients with Ph+ ALL.
This category includes MaHR, PCyR, CCyR, and MMR.
This category includes PCyR, CCyR, and MMR.
Seven deaths were assessed by investigators as possibly or probably related to ponatinib (CP-CML: pneumonia, acute myocardial infarction; AP-CML: fungal pneumonia, gastrointestinal hemorrhage; BP-CML: hemorrhagic gastritis; Ph+ ALL: cardiac arrest, mesenteric arterial occlusion).
Patients who continued to derive clinical benefit from their treatment had the option to receive ponatinib through alternative mechanisms.
This category includes stem cell transplantation (in 11 patients with CP-CML, 5 with AP-CML, 6 with BP-CML, and 1 with Ph+ ALL). The 9 CP-CML patients and 1 AP-CML patient who remained on study at the time of last response assessment are not included in this category.