Table 3.
Response to Therapy by Disease State and Prior Treatment With TKIs
| AP CML | BP CML | ||||||
|---|---|---|---|---|---|---|---|
| Response, n (%) | 2L (n = 49) | ≥3L (n = 30) | Total (n = 79) | 2L (n = 36) | ≥3L (n = 28) | Total (n = 64) | ALL (n = 24) |
| Week 48 hematologic responsea | |||||||
| Evaluable patientsb | 43 | 29 | 72 | 34 | 26 | 60 | 22 |
| OHR [95% CI] | 29 (67) [52–81] | 12 (41) [24–61] | 41 (57) [45–69] | 13 (38) [22–56] | 4 (15) 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 | 17 (28) 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 | 1 (5) [<1–23] |
| Cumulative hematologic response by 4 yrs | |||||||
| Evaluable patientsa ,b | 43 | 29 | 72 | 34 | 26 | 60 | 22 |
| OHR [95% CI] | 29 (67) [52%–81%] | 12 (41) [24%–61%] | 41 (57) [45%–69%] | 13 (38) [22%–56%] | 4 (15) [4%–35%] | 17 (28) [18%–41%] | 2 (9) [1%–29%] |
| MHR | 23 (54) | 11 (38) | 34 (47) | 9 (27) | 2 (8) | 11 (18) | 2 (9) |
| CHR | 17 (40) | 7 (24) | 24 (33) | 9 (27) | 1 (4) | 10 (17) | 2 (9) |
| Median [range] time to OHRc (wk) | 12.0 [3.7–49.0] | 12.1 [4.0–24.0] | 12.0 [3.7–49.0] | 8.0 [4.0–12.0] | 11.6 [4.1–12.1] | 8.9 [4.0–12.1] | 43.6 [4.0–83.1] |
| Evaluable patients without a CHR at baseline | 39 | 24 | 63 | 32 | 23 | 55 | 21 |
| OHR | 22 (57) | 7 (29) | 29 (46) | 9 (28) | 1 (4) | 10 (18) | 1 (5) |
| Cumulative cytogenetic response by 4 years | |||||||
| Evaluable patientsa ,d | 46 | 26 | 72 | 30 | 24 | 54 | 20 |
| MiCyR | 3 (7) | 0 | 3 (4) | 1 (3) | 1 (4) | 2 (4) | 0 |
| MCyR [95% CI] | 22 (48)d [33%–63%] | 7 (27) [12%–48%] | 29 (40)d [29%–53%] | 15 (50) [31%–69%] | 5 (21)e [7%–42%] | 20 (37)e [24%–51%] | 4 (20) [6%–44%] |
| CCyR | 16 (35) | 6 (23) | 22 (31) | 11 (37) | 4 (17) | 15 (28) | 4 (20) |
| Median [range] time to MCyRc (wk) | 12.3 [3.9–42.0] | 144.7 [4.0–144.7] | 24.0 [3.9–144.7] | 12.1 [3.9–25.1] | NR [4.1–12.3] | 12.1 [3.9–25.1] | 9.0 [4.0–12.0] |
| Evaluable patients without a CCyR at baseline | 46 | 23 | 69 | 28 | 22 | 50 | 18 |
| MCyR | 22 (48) | 4 (17) | 26 (38) | 13 (46) | 3 (14) | 16 (32) | 3 (17) |
To be considered a responder, the patient must have improved from their baseline assessment or maintained their baseline response.
Evaluable patients included those who received ≥1 dose of bosutinib and had a valid baseline hematologic measurement.
Time to response was calculated among responders from first study dosing to the earliest date of response (confirmed response for OHR and unconfirmed response for MCyR).
Evaluable patients included those who received ≥1 dose of bosutinib and had a valid baseline cytogenetic measurement.
Included four patients with a partial cytogenetic response determined by using FISH instead of cytogenetic analysis.
Included one patient with CCyR determined by using FISH instead of cytogenetic analysis.
2L, second‐line (prior imatinib only); ≥3L, third‐/fourth‐line (imatinib followed by dasatinib and/or nilotinib); AP, accelerated phase; CML, chronic myeloid leukemia; BP, blast phase; ALL, acute lymphoblastic leukemia; OHR, overall hematologic response; CI, confidence interval; CHR, complete hematologic response; MiCyR, minor cytogenetic response; MCyR, major cytogenetic response; CCyR, complete cytogenetic response.