Table 2.
Baseline predictors of cytogenetic response
| Baseline Characteristic | OR (95% CI)a | ||
|---|---|---|---|
| 3 Months | 6 Months | Cumulative | |
| Age ≥65 years (n = 61) vs. <65 years (n = 202) | |||
| MCyR |
0·35 (0·16–0·79) P = 0·0107 |
0·80 (0·38–1·68) NS |
0·62 (0·31–1·25) NS |
| CCyR |
0·50 (0·20–1·23) NS |
0·57 (0·24–1·34) NS |
0·69 (0·34–1·41) NS |
| Women (n = 122) vs. men (n = 141) | |||
| MCyR |
0·79 (0·42–1·49) NS |
0·58 (0·31–1·07) NS |
0·55 (0·30–0·98) P = 0·0438 |
| CCyR |
0·39 (0·18–0·86) P = 0·0195 |
0·33 (0·16–0·71) P = 0·0046 |
0·61 (0·33–1·10) NS |
| Prior IM response: yes (n = 140) vs. no (n = 84)b | |||
| MCyR |
4·88 (2·06–11·60) P = 0·0003 |
2·84 (1·37–5·91) P = 0·0052 |
2·36 (1·21–4·61) P = 0·0119 |
| CCyR |
9·26 (1·88–45·70) P = 0·0063 |
20·84 (4·46–97·32) P = 0·0001 |
3·49 (1·72–7·05) P = 0·0005 |
| Prior IM response: unknown (n = 39) vs. no (n = 84)b | |||
| MCyR |
4·79 (1·55–14·75) P = 0·0064 |
1·94 (0·71–5·28) NS |
1·74 (0·70–4·33) NS |
| CCyR |
16·71 (2·73–102·36) P = 0·0023 |
20·28 (3·53–116·45) P = 0·0007 |
3·43 (1·32–8·92) P = 0·0117 |
| % Ph+ cells: <95% to >35% (n = 65) vs. ≤35% (n = 45)c | |||
| MCyR |
0·38 (0·16–0·95) P = 0·0383 |
0·43 (0·16–1·13) NS |
0·55 (0·19–1·59) NS |
| CCyR |
0·20 (0·08–0·52) P = 0·0009 |
0·19 (0·07–0·53) P = 0·0015 |
0·27 (0·10–0·76) P = 0·0133 |
| % Ph+ cells: ≥95% (n = 124) vs. ≤35% (n = 45)c | |||
| MCyR |
0·20 (0·08–0·51) P = 0·0007 |
0·15 (0·06–0·40) P = 0·0001 |
0·16 (0·06–0·45) P = 0·0005 |
| CCyR |
0·05 (0·02–0·16) P ≤ 0·0001 |
0·06 (0·02–0·18) P ≤ 0·0001 |
0·10 (0·03–0·27) P ≤ 0·0001 |
| % Ph+ cells: Unknown (n = 29) vs. ≤35% (n = 45)c | |||
| MCyR |
0·16 (0·04–0·65) P = 0·0107 |
0·12 (0·03–0·46) P = 0·0019 |
0·20 (0·06–0·71) P = 0·0124 |
| CCyR |
0·04 (0·004–0·37) P = 0·0046 |
0·08 (0·02–0·41) P = 0·0026 |
0·17 (0·05–0·60) P = 0·0062 |
| Prior IM resistance: yes (n = 182) vs. no (n = 81) | |||
| MCyR |
0·76 (0·37–1·60) NS |
0·73 (0·35–1·51) NS |
1·12 (0·55–2·29) NS |
| CCyR |
0·10 (0·41–2·44) NS |
0·79 (0·33–1·88) NS |
1·29 (0·63–2·66) NS |
| IFNα treatment before IM or diagnosis to IM initiation ≥6 months [n = 134] vs. <6 months [n = 129] | |||
| MCyR |
0·11 (0·03–0·41) P = 0·0009 |
0·16 (0·05–0·51) P = 0·0018 |
0·47 (0·19–1·16) NS |
| CCyR |
0·08 (0·02–0·43) P = 0·0032 |
0·09 (0·02–0·39) P = 0·0015 |
0·46 (0·18–1·19) NS |
| Prior IFNα: yes (n = 89) vs. no (n = 174) | |||
| MCyR |
5·66 (1·78–17·93) P = 0·0032 |
5·58 (1·97–15·81) P = 0·0012 |
3·66 (1·55–8·66) P = 0·0031 |
| CCyR |
5·26 (1·15–23·94) P = 0·0319 |
7·85 (2·00–30·84) P = 0·0032 |
3·32 (1·35–8·21) P = 0·0092 |
| BCR‐ABL1 mutation status: sensitive mutation (n = 26) vs. no mutation (n = 119)d | |||
| MCyR |
1·56 (0·51–4·75) NS |
1·46 (0·51–4·20) NS |
1·07 (0·37–3·08) NS |
| CCyR |
1·05 (0·26–4·16) NS |
2·95 (0·85–10·26) NS |
0·74 (0·26–2·11) NS |
| BCR‐ABL1 mutation status: insensitive mutation (n = 28) vs. no mutation (n = 119)d | |||
| MCyR |
0·79 (0·24–2·56) NS |
0·80 (0·27–2·40) NS |
0·66 (0·25–1·76) NS |
| CCyR |
1·40 (0·35–5·72) NS |
1·35 (0·36–5·11) NS |
0·78 (0·29–2·11) NS |
| BCR‐ABL1 mutation status: unknown sensitivity mutation (n = 23) vs. no mutation (n = 119)d | |||
| MCyR |
1·79 (0·55–5·81) NS |
1·47 (0·46–4·71) NS |
0·69 (0·23–2·09) NS |
| CCyR |
2·05 (0·53–8·00) NS |
2·41 (0·62–9·43) NS |
0·69 (0·22–2·14) NS |
| BCR‐ABL1 mutation status: unknown/missing mutation (n = 67) vs. no mutation (n = 119)d | |||
| MCyR |
0·73 (0·34–1·57) NS |
0·89 (0·42–1·87) NS |
0·63 (0·31–1·29) NS |
| CCyR |
0·50 (0·19–1·31) NS |
1·13 (0·47–2·76) NS |
0·59 (0·28–1·23) NS |
| Disease duration, years | |||
| MCyR |
1·05 (0·92–1·20) NS |
1·03 (0·90–1·16) NS |
0·98 (0·88–1·10) NS |
| CCyR |
1·04 (0·88–1·23) NS |
1·01 (0·86–1·19) NS |
0·98 (0·87–1·11) NS |
| Basophils, % | |||
| MCyR |
0·95 (0·86–1·06) NS |
0·95 (0·87–1·04) NS |
1·03 (0·95–1·12) NS |
| CCyR |
1·06 (0·94–1·19) NS |
1·02 (0·91–1·14) NS |
1·03 (0·95–1·12) NS |
CCyR, complete cytogenetic response; CML, chronic myeloid leukaemia; CP, chronic phase; FISH, fluorescence in situ hybridization; IM, imatinib; MCyR, major cytogenetic response; NS, not significant (P > 0·05); IFNα, interferon‐α; Ph+, Philadelphia chromosome–positive; OR, odds ratio; 95%CI, 95% confidence interval.
Note: 1 patient with a missing value for a baseline covariate was not included in any of the predictors analyses.
Odds ratios >1 and hazard ratios <1 indicate better outcome for group 1 vs. group 2. P values were not adjusted for multiple comparisons.
Prior response was defined as achievement of at least a minimal cytogenetic response (standard cytogenetic criteria: 66% to 95% Ph+ cells from bone marrow or BCR‐ABL1 from FISH).
Required ≥20 metaphases for standard cytogenetics or ≥200 cells for FISH.
Bosutinib‐sensitive mutations are those resulting in half maximal inhibitory concentration (IC50) ≤2‐fold higher than wild type (M244V, Q252H, Y253H/F, D276G, E279K, E292L, M343T, M351T, F359V, L384M, H396P/R and G398R) and bosutinib‐insensitive mutations are those resulting in IC50 values >2‐fold higher than wild type (L248R/V, G250E, E255K/V, V299L, T315A/I/V, F317L/R/V, F359I and F486S); the sensitivities of all other mutations are unknown. If patients had >1 mutation with different sensitivities, they were categorized based on the following hierarchy: bosutinib‐insensitive, unknown sensitivity and bosutinib‐sensitive (Redaelli et al, 2009, 2012).