Table 4.
Data on response to treatment and long-term outcomes according to transcript type in patients treated with different TKIs types, including newer-generation TKIs.
| Ref. | TKI | No. of pts | FU | CCyR Rate e13a2 vs. e14a2 | MMR Rate e13a2 vs. e14a2 | DMR Rate e13a2 vs. e14a2 | OS Rate e13a2 vs. e14a2 | PFS/TFS/EFS/FFS Rate e13a2 vs. e14a2 |
|---|---|---|---|---|---|---|---|---|
| Jain et al. [91] | ima, das, nilo | 481 | 8 y | At 6 mos, 73% vs. 81% | At 1 y, 55% vs. 83% | At 12 mos, MR4.5 19% vs. 42% At 18 mos, MR4.5 28% vs. 50% At 60 mos, MR4.5 47% vs. 69% |
NS | TFS at 5 y, 91% vs. 97% (p = 0.01) EFS at 5 y, 79% vs. 89% (p = 0.09); HR of e14a2 to e13a2 = 0.59 (95% CI 0.36–0.98; p = 0.04) |
| Sasaki et al. [108] | ima, das, nilo, pona | 603 | 8.5 y | NS | At 1 y, 36% vs. 46% | sMR4.5, 34% vs. 45% | NR | NR |
| D’adda et al. [109] | ima, das, nilo | 173 | 5 y | NS | NS | MR4.0, 52% vs. 82% (p = 0.008) sDMR, 27% vs. 47% (p = 0.004) a |
NR | NR |
| Shanmuganathan et al. [110] | NR | 280 | NR | NR | NR | At 6 y, MR4.5, 52% vs. 70% | NR | NR |
| Abdulla et al. [114] | ima, das, nilo, pona | 79 | 2.5 y | NS | NS | NS | NR | NR |
| Su et al. [111] | ima, das, nilo | 1124 | 4 y | At 1 y, cumulative incidence of CCyR: with ima, 45% vs. 59% (p = 0.001) with das, NS with nilo, 70% vs. 83% (p = 0.041) |
At 1 y: b with ima, 27% vs. 38% (p = 0.010) with das, NS with nilo, 58% vs. 84% (p = 0.002) |
At 1 y, NS (with any TKI) | At 5 y, NS (with any TKI) | PFS at 5 y, NS (with any TKI) |
| Genthon et al. [112] | nilo | 118 | 4 y | NS | At 1 y, 50% vs. 67% (p = 0.048) | Cumulative incidence of MR4.5, 60% vs. 100% (p = 0.005) | NS | EFS, NS |
| Castagnetti et al. [113] | nilo | 345 | 5 y | NR | NS c | At 3 y, MR4.0, 56% vs. 66% (p = 0.06) c | NS | PFS, NS |
| Jain et al. [116] | pona | 85 (38 frontline, 47 RR) | NR | Among RR pts, 50% vs. 61% | Among RR pts, 29% vs. 52% | Among frontline pts, the median levels of transcripts at 3 and 6 mos, NS | At 3 y, among RR pts, 62% vs. 100% (p = 0.03) | Among RR pts, FFS at 3 y, 54% vs. 87% (p = 0.08) |
The reported data include patients treated with frontline TKI expressing the e13a2 or e14a2 transcript (whether alone or in co-expression with the e13a2). Pts patients, Ima imatinib, Das dasatinib, Nilo nilotinib, Pona ponatinib, FU follow-up, CCyR complete cytogenetic response, MMR major molecular response (BCR-ABL1 ≤ 0.1%IS), DMR deep molecular response (MR4.0, BCR-ABL1 ≤ 0.01%IS; MR4.5, BCR-ABL1 ≤ 0.0032%IS), sDMR stable DMR, sMR4.0 stable MR4.0, sMR4.5 stable MR4.5, Y years, Mos months, HR Hazard Ratio, CI confidence interval, OS Overall Survival, PFS progression-free survival, TFS transformation-free survival, EFS event-free survival, FFS failure-free survival, RR relapsed/refractory, NS not significant with p > 0.1, NR not reported. a In this study, the achievement of a sDMR was significantly lower in patients treated with imatinib compared to those who received frontline 2GTKIs in both the e13a2 and e14a2 cohorts (p = 0.0485 and p = 0.0006, respectively). b In this study, the cumulative incidences of MMR at 12, 24, 36 and 60 months were significantly higher in patients treated with 2G-TKIs compared to those treated with imatinib in both the e13a2 and e14a2 cohorts (p < 0.01), in the absence of significant differences between nilotinib and dasatinib groups. c In this study, when grouping together the patients with the e14a2 transcript alone and those co-expressing both transcripts and comparing them to patients with e13a2 transcript alone, the response differences became significant (cumulative incidence of MMR and MR4.0, p = 0.050 and p = 0.036, respectively), in the absence of outcome differences (PFS and OS, p = 0.340 and p = 0.276, respectively).