Table 2.
CR induction results from representative series of adult/elderly Ph+ ALL, by type of TKI and associated induction drugs. Reports from randomized trials are marked with an asterisk (*)
| Study (author, ref.) | No. of patients | Patient median age, years (range)1,2 | TKI | Associated drug regimen | Induction results (%) | ||
|---|---|---|---|---|---|---|---|
| CR | NR | ED | |||||
| TKI + intensive chemotherapy | |||||||
| Yanada (2006) [59] | 80 | 48 (15–63) | IM | JALSG ALL202 | 96.2 | 1.3 | 2.5 |
| Wassmann (2006) [60] | 45 | 41 (19–63) | IM | GMALL | 96 | 2 | – |
| Ottmann (2007) [61]* | 27 | 68 (58–78)2 | IM | GMALL (intensive arm) | 85 | 7 | 8 |
| De Labarthe (2007) [62] | 45 | (16–59) | IM | GRAAPH-2003 | 93.5 | – | 6.5 |
| Pfeifer (2010) [63] | 284 | 43 (17–65) | IM | GMALL | 87 | 4.2 | 8.8 |
| Bassan (2011) [64] | 59 | 45 (20–66) | IM | NILG 09/00 | 92 | 4 | 4 |
| Ribera (2012) [65] | 59 | 40 (15–62) | IM | PETHEMA | 95.5 | 1.5 | 3 |
| Thyagu (2012) [66] | 32 | 46 (18–60) | IM | DFCI modified | 93.7 | 6.3 | – |
| Fielding (2014) [67] | 89 | 42 (16–64) | IM | UKALL XII/ECOG 2993 | 92 | 1 | 7 |
| Chalandon (2015) [68]* | 133 | 45 (18–59) | IM | Hyper-CVAD (intensive arm) | 91 | 2.2 | 6.7 |
| Daver (2015) [69] | 45 | 51 (17–84) | IM | Hyper-CVAD | 93 | 3.5 | 3.5 |
| Lim (2015) [70] | 87 | 41 (16–71) | IM | Multiagent | 94 | – | 6 |
| Wang (2018) [71] | 145 | 37 (14–65) | IM | CODP | 94 | 4 | 2 |
| Ravandi (2015) [72] | 72 | 55 (21–80) | DAS | Hyper-CVAD | 96 | – | 4 |
| Kim (2015) [73] | 90 | 47 (17–71) | NIL | Multiagent intensive | 91 | – | 9 |
| Ravandi (2016) [74] | 94 | 44 (20–60) | DAS | Hyper-CVAD | 88 | 9 | 23 |
| Jabbour (2018) [75] | 76 | 47 (39–71) | PON | Hyper-CVAD | 1004 | – | – |
| TKI+ non-intensive chemotherapy | |||||||
| Bassan (2010) [64] | 675 | – | IM | Low intensity | 100 | – | – |
| Chalandon (2015) [68]* | 135 | 49 (18–59) | IM | Low intensity (non-intensive arm) | 98.56 | 0.7 | 0.7 |
| Rousselot (2016) [76] | 71 | 69 (59–83)2 | DAS | Low intensity | 96 | 1 | 3 |
| Chalandon (2018) [77] | 60 | 47 (18–59) | NIL | Low intensity (non-intensive arm) | 98.3 | – | 1.7 |
| Ottmann (2018) [78] | 72 | 65 (55–85)2 | NIL | Low intensity | 94.4 | 2.8 | 2.8 |
| TKI without chemotherapy (prednisone only) | |||||||
| Vignetti (2007) [79] | 29 | 69 (61–83)2 | IM | Prednisone | 100 | – | – |
| Ottmann (2007) [61]* | 28 | 66 (54–79)2 | IM | – | 967 | 4 | – |
| Foà (2011) [80] | 53 | 54 (24–76) | DAS | Prednisone | 100 | – | – |
| Papayannidis (2013) [81] | 36 | 66 (28–84) | IM/NIL8 | Prednisone | 94 | 6 | – |
| Chiaretti (2015) [58] | 60 | 42 (18–59) | DAS | Prednisone | 96.6 | 3.4 | – |
| Chiaretti (2016) [82] | 49 | 46 (17–59) | IM | Prednisone | 96 | – | 4 |
| Martinelli (2017) [83] | 42 | 68 (27–85)2 | PON | Prednisone | 95.2 | NA | NA |
1Including elderly (> 55 years) and/or frail patients only
2Two patients not in CR by week 6
3All 65 patients with active disease at enrolment
4From modified NILG 09/00 protocol (low-intensity induction: no L-asparaginase, 50% idarubicin reduction; data on file)
5Randomized phase 3 trial: higher CR rate in the non-intensive arm (P = 0.006) due to lower ED rate (P = 0.010)
6P = 0.001 for CR rate vs intensive chemotherapy arm
7Alternating schedule (every 6 weeks)
8Two patients entering CR by day 57, losing response by day 85
Abbreviations: IM imatinib, DAS dasatinib, NIL nilotinib, PON ponatinib, CR complete remission, NR non-responsive, ED early death, NA not available