Table 1.
Summary characteristics for the 21 eligible RCTs (10,187 patients)
| Study Year | Journal Ref | Trial Number | Study Design | Treatment | Patients (N) | Male (%) | Age (yr) | Risk Group (%) | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sokal risk | Hasford risk | ||||||||||||
| low | mid | high | low | mid | high | ||||||||
| O’Brien (1) 2003 | N Engl J Med [21–23] |
NCT 00006343 |
Phase III, randomized, open-label, multicenter (IRIS) | Imatinib 400 mg qd | 553 | 56.0 | 50(18–70) | 53 | 29 | 18 | 46 | 44 | 10 |
| IFN-α + Ara-C | 553 | 61.0 | 51(18–70) | 47 | 30 | 22 | 45 | 45 | 10 | ||||
| Cortes (1) 2009 | J Clin Oncol [24] |
NCT 00124748 |
Phase III, randomized, multicenter | Imatinib 800 mg qd | 319 | 57.4 | 48(18–75) | 42.3 | 34.8 | 23.0 | / | / | / |
| Imatinib 400 mg qd | 157 | 53.5 | 45(18–75) | 39.5 | 33.8 | 27.0 | / | / | / | ||||
| Baccarani 2009 | Blood [25] |
NCT 00514488 |
Randomized, multicenter | Imatinib 800 mg qd | 108 | 55.0 | 51(18–84) | / | / | / | / | / | / |
| Imatinib 400 mg qd | 108 | 57.0 | 51(18–81) | / | / | / | / | / | / | ||||
| Preudhomme 2010 | N Engl J Med [26] |
NCT 00219739 |
Phase III, randomized (SPIRIT) | Imatinib 400 mg qd | 159 | 69.0 | 50 | 38 | 38 | 24 | / | / | / |
| Imatinib 600 mg qd | 160 | 56.0 | 51 | 37 | 38 | 28 | / | / | / | ||||
| Imatinib 400 mg qd + Ara-C | 158 | 58.0 | 55 | 37 | 41 | 23 | / | / | / | ||||
| Imatinib 400 mg qd + IFN-α | 160 | 65.0 | 51 | 36 | 40 | 24 | / | / | / | ||||
| Saglio 2010 | N Engl J Med [27–30] |
NCT 00471497 |
Phase III, randomized, open-label, multinational, multicenter (ENESTnd) | Nilotinib 300 mg bid | 282 | 56.0 | 47(18–85) | 37 | 36 | 28 | / | / | / |
| Nilotinib 400 mg bid | 281 | 62.0 | 47(18–81) | 37 | 36 | 28 | / | / | / | ||||
| Imatinib 400 mg qd | 283 | 56.0 | 46(18–80) | 37 | 36 | 28 | / | / | / | ||||
| Kantarjian 2010 | N Engl J Med [31–35] |
NCT 00481247 |
Phase III, randomized, multicenter (DASISION) | Dasatinib 100 mg qd | 259 | 56.0 | 46(18–84) | / | / | / | 33 | 48 | 19 |
| Imatinib 400 mg qd | 260 | 63.0 | 49(18–78) | / | / | / | 33 | 47 | 19 | ||||
| Petzer 2010 | Haematologica [36] |
NCT 00327262 |
Randomized, multinational, multicenter (ISTAHIT) | Imatinib 800 mg qd | 113 | 46.5 | 46(18–76) | / | / | / | / | / | / |
| Imatinib 400 mg qd | 113 | 42.5 | 46(20–68) | / | / | / | / | / | / | ||||
| Cortes (2) 2011 | Blood [37–39] |
NCT 00574873 |
Randomized, multinational, multicenter (BELA) | Bosutinib 500 mg qd | 250 | 60.0 | 48(19–91) | 35 | 47 | 18 | / | / | / |
| Imatinib 400 mg qd | 252 | 54.0 | 47(18–89) | 35 | 47 | 18 | / | / | / | ||||
| Hehlmann (1) 2011 | J Clin Oncol [40] | / | Randomized, multinational, multicenter | Imatinib 800 mg qd | 338 | 59.0 | 52(18–86) | / | / | / | / | / | / |
| Imatinib 400 mg qd | 325 | 60.0 | 64(16–88) | / | / | / | / | / | / | ||||
| Imatinib 400 mg qd + IFN-α | 351 | 61.0 | 54(16–83) | / | / | / | / | / | / | ||||
| Radich 2012 | Blood [41] |
NCT 00070499 |
Phase III, randomized, multinational, multicenter | Dasatinib 100 mg qd | 123 | 60.0 | 47(18–90) | / | / | / | 36 | 33 | 32 |
| Imatinib 400 mg qd | 123 | 59.0 | 50(19–89) | / | / | / | 36 | 37 | 28 | ||||
| Thielen 2013 | Ann Hematol [42] | NTR674 | Phase III, randomized, multicenter | Imatinib 400 mg qd | 55 | NA | 46(17–65) | 29 | 44 | 22 | / | / | / |
| Imatinib 400 mg qd + Ara-C | 54 | NA | 45(23–65) | 37 | 39 | 20 | / | / | / | ||||
| Hughes 2014 | Blood [43] |
NCT 00760877 |
Phase III, randomized, open-label, multicenter (ENESTcmr) | Nilotinib 400 mg bid | 104 | 68.3 | 46(23–82) | / | / | / | / | / | / |
| Imatinib 400 mg qd | 103 | 63.1 | 52(19–76) | / | / | / | / | / | / | ||||
| O’Brien (2) 2014 | Blood [44, 45] | / | Phase III, randomized, multinational, multicenter (SPIRIT2) | Dasatinib 100 mg qd | 407 | 61.0 | 53(18–89) | / | / | / | / | / | / |
| Imatinib 400 mg qd | 407 | 60.0 | 53(18–87) | / | / | / | / | / | / | ||||
| Deininger 2014 | Br J Hematol [46] |
NCT 00070499 |
Phase II, randomized | Imatinib 800 mg qd | 73 | 64.0 | 52(19–82) | / | / | / | 21 | 30 | 49 |
| Imatinib 400 mg qd | 72 | 63.0 | 50(23–80) | / | / | / | 21 | 30 | 49 | ||||
| Hjorth-Hansen 2015 | Eu J Hematol [47] |
NCT 00852566 |
Phase II, randomized multicenter (NordCML006) | Dasatinib 100 mg qd | 22 | 32.0 | 53(29–71) | 32 | 45 | 23 | / | / | / |
| Imatinib 400 mg qd | 24 | 63.0 | 58(38–78) | 49 | 34 | 17 | / | / | / | ||||
| Wang 2015 | Blood [48] |
NCT 01275196 |
Phase III, randomized, multicenter | Nilotinib 300 mg bid | 134 | 68.0 | 41(18–76) | 51 | 33 | 16 | / | / | / |
| Imatinib 400 mg qd | 133 | 61.0 | 39(19–74) | 52 | 32 | 16 | / | / | / | ||||
| Kwak 2015 | Blood [49] |
NCT 01511289 |
Phase III, randomized, open-label, multicenter (RERISE) | Radotinib 300 mg bid | 79 | 66.0 | 45(20–75) | 27 | 48 | 25 | / | / | / |
| Radotinib 400 mg bid | 81 | 58.0 | 43(18–84) | 27 | 48 | 25 | / | / | / | ||||
| Imatinib 400 mg qd | 81 | 64.0 | 45(18–83) | 27 | 48 | 37 | / | / | / | ||||
| Lipton 2016 | Lancet Oncol [50] |
NCT 01650805 |
Phase III, randomized, open-label, multicenter | Ponatinib 45 mg qd | 155 | 63.0 | 55(18–89) | 41 | 41 | 17 | / | / | / |
| Imatinib 400 mg qd | 152 | 61.0 | 52(18–86) | 41 | 44 | 15 | / | / | / | ||||
| Cortes (3) 2016 | Lancet Haematol [51] |
NCT 00802841 |
Phase III, randomized, multicenter (LASOR) | Nilotinib 400 mg bid | 96 | 56.0 | 46(32–46) | / | / | / | / | / | / |
| Imatinib 600 mg qd | 95 | 61.0 | 44(33–56) | / | / | / | / | / | / | ||||
| Hehlmann (2) 2017 | Leukemia [52, 53] |
NCT 00055874 |
Randomized, open-label, multinational, multicenter | Imatinib 400 mg qd | 400 | 61.0 | 53(16–88) | 36 | 40 | 25 | / | / | / |
| Imatinib 400 mg qd + IFN-α | 430 | 59.0 | 53(16–83) | 39 | 39 | 22 | / | / | / | ||||
| Imatinib 400 mg qd + Ara-C | 158 | 63.0 | 52(18–79) | 39 | 34 | 27 | / | / | / | ||||
| Imatinib 400 mg qd after IFN-α | 128 | 63.0 | 53(18–87) | 40 | 45 | 15 | / | / | / | ||||
| Imatinib 800 mg qd | 420 | 59.0 | 51(18–85) | 37 | 37 | 27 | / | / | / | ||||
| Cortes (4) 2018 | J Clin Oncol [54] |
NCT 02130557 |
Phase III, randomized, open-label, multicenter | Bosutinib 400 mg qd | 268 | 57.7 | 52(18–84) | 38 | 41 | 201 | / | / | / |
| Imatinib 400 mg qd | 268 | 56.0 | 53(19–84) | 40 | 39 | 21 | / | / | / | ||||
(“/” means “not available”)