Select studies of second- and third-generation TKIs for Ph+ ALL
| Group (study) . | Low-intensity induction? . | Phase . | Regimen . | N . | Age in years, median (range) . | CMR (%) . | alloHCT, CR1 (%) . | DFS/RFS/ EFS (%) . | OS (%) . |
|---|---|---|---|---|---|---|---|---|---|
| GIMEMA(Italy) LAL1205 NCT00391989 2006-2008 | Yes | 2 | Ind: DAS, pred Cons: per investigator | 53 | 54 (24-77) | 23 (best) | 34 | 51 (1.7-yr DFS) | 69 (1.7 yr) |
| MDACC(US) NCT00390793 2006-2012 | No | 2 | Ind/cons: DAS + hyper-CVAD | 72 (63a) | 55 (21-80) | 65 (best) | 17 | 42 (5-yr EFS) 44 (5-yr DFS) | 46 (5 yr) |
| EWALL(Europe) Ph01 NCT02888977 2007-2010 | Yes | 2 | Ind: DAS, vinc, dex Cons: DAS, low-int chemo | 71 | 69 (59-83) | 24 (MRD2) | 10 | 27 (5-yr EFS) 28 (5-yr RFS) | 36 (5 yr) |
| SWOG (US) SWOG 0805 NCT00792948 2009-2013 | No | 2 | DAS + hyper-CVAD | 94 (60a) | 44 (20-60) | - | 52 | 55 (3-yr EFS) 62 (3-yr RFS) | 69 (3 yr) |
| CALGB(US) C10701 NCT01256398 2010-2014 | Yes | 2 | Ind: DAS, dex Cons: alloHSCT or autoHSCT; or chemo (>70 yrs) | 65 | 60 (22-87) | 40 (end course IV) | 48 | 37 (5-yr DFS) | 48 (5 yr) |
| GIMEMA(Italy) TOTAL Therapy LAL1509 NCT03318770 2011-2013 | Yes | 2 | Ind: DAS, pred Cons: if CMR → DAS; no CMR → DAS plus HSCT or chemo | 60 | 42 (19-59) | 18 (end ind) | 37 | 47 (5-yr DFS) | 56 (5 yr) |
| DFCI DF/HCC 18-170 2018-2022 | Yes | 1 | Ind: DAS, ASC, pred Cons: DAS, ASC | 22 | 64 (33-85) | - | 33 | 63 (2-yr EFS) | 75 (2 yr) |
| KAALLWP(Korea) NCT00844298 2009-2012 | No | 2 | Ind/cons: NIL + chemo | 90 | 46 (17-71) | 86 (best) | 63 | 72 (2-yr RFS) | 72 (2 yr) |
| EWALL(Europe) Ph02 NCT01528085 2012-2020 | Yes | 2 | Ind: NIL, vinc, pred Cons: NIL, low-int chemo | 72 | 65 (55-85) | 14 (end ind) 58 (end cons) | 33 | 42 (4-yr EFS) | 47 (4 yr) |
| GRAALL(SAKK) GRAAPH-2014 NCT02611492 2015-2019 | Yes | 3 | Ind: NIL, vinc, pred Cons: NIL + high- (A) vs. low- (B) int chemo (1:1) | 156 | 47 (39-54 IQR) | 26 (TP4) | 60 | A: 76 (4-yr RFS) B: 58 (4-yr RFS) p = 0.028 | A: 79 (4 yr) B: 72 (4 yr) p = 0.88 |
| MDACC(US) NCT01424982 2011-2019 | No | 2 | PON + hyper-CVAD | 86 (66a) | 46 (21-80) | 87 (best) | 23 | 65 (6-yr EFS) 80 (6-yr DFS) | 75 (6 yr) |
| GIMEMA(Italy) INCB4344-20/ LAL1811 NCT01641107 2014-2017 | Yes | 2 | PON + pred | 44 | 67 (26-85); 80% ≥ 60 yrs | 41 (week 24) 82% (overall) | 14 | 14.3 mo (med, EFS) | NR (median) |
| PETHEMA(Spain) PONAFIL NCT02776605 2017-2020 | No | 2 | PON + high- int chemo | 30 | 49 (19-59) | 47 (ind) 71% (cons) | 87 | 70 (3-yr EFS) | 96 (3 yr) |
| PhALLCON (Global) NCT03589326 2018-2022 | Yes | 3 | PON vs IM + low-int chemo (2:1) | 245 | 54 | MR4.5 after C9 46 (PON) 26 (IM) | 31 (PON) 37 (IM) | Med EFS 29.0 Med EFS NR (HR 0.65, 95% CI 0.39-1.1) | Med OS NR Med OS NR (HR 0.76, 95% CI 0.38-1.52) |
| Group (study) . | Low-intensity induction? . | Phase . | Regimen . | N . | Age in years, median (range) . | CMR (%) . | alloHCT, CR1 (%) . | DFS/RFS/ EFS (%) . | OS (%) . |
|---|---|---|---|---|---|---|---|---|---|
| GIMEMA(Italy) LAL1205 NCT00391989 2006-2008 | Yes | 2 | Ind: DAS, pred Cons: per investigator | 53 | 54 (24-77) | 23 (best) | 34 | 51 (1.7-yr DFS) | 69 (1.7 yr) |
| MDACC(US) NCT00390793 2006-2012 | No | 2 | Ind/cons: DAS + hyper-CVAD | 72 (63a) | 55 (21-80) | 65 (best) | 17 | 42 (5-yr EFS) 44 (5-yr DFS) | 46 (5 yr) |
| EWALL(Europe) Ph01 NCT02888977 2007-2010 | Yes | 2 | Ind: DAS, vinc, dex Cons: DAS, low-int chemo | 71 | 69 (59-83) | 24 (MRD2) | 10 | 27 (5-yr EFS) 28 (5-yr RFS) | 36 (5 yr) |
| SWOG (US) SWOG 0805 NCT00792948 2009-2013 | No | 2 | DAS + hyper-CVAD | 94 (60a) | 44 (20-60) | - | 52 | 55 (3-yr EFS) 62 (3-yr RFS) | 69 (3 yr) |
| CALGB(US) C10701 NCT01256398 2010-2014 | Yes | 2 | Ind: DAS, dex Cons: alloHSCT or autoHSCT; or chemo (>70 yrs) | 65 | 60 (22-87) | 40 (end course IV) | 48 | 37 (5-yr DFS) | 48 (5 yr) |
| GIMEMA(Italy) TOTAL Therapy LAL1509 NCT03318770 2011-2013 | Yes | 2 | Ind: DAS, pred Cons: if CMR → DAS; no CMR → DAS plus HSCT or chemo | 60 | 42 (19-59) | 18 (end ind) | 37 | 47 (5-yr DFS) | 56 (5 yr) |
| DFCI DF/HCC 18-170 2018-2022 | Yes | 1 | Ind: DAS, ASC, pred Cons: DAS, ASC | 22 | 64 (33-85) | - | 33 | 63 (2-yr EFS) | 75 (2 yr) |
| KAALLWP(Korea) NCT00844298 2009-2012 | No | 2 | Ind/cons: NIL + chemo | 90 | 46 (17-71) | 86 (best) | 63 | 72 (2-yr RFS) | 72 (2 yr) |
| EWALL(Europe) Ph02 NCT01528085 2012-2020 | Yes | 2 | Ind: NIL, vinc, pred Cons: NIL, low-int chemo | 72 | 65 (55-85) | 14 (end ind) 58 (end cons) | 33 | 42 (4-yr EFS) | 47 (4 yr) |
| GRAALL(SAKK) GRAAPH-2014 NCT02611492 2015-2019 | Yes | 3 | Ind: NIL, vinc, pred Cons: NIL + high- (A) vs. low- (B) int chemo (1:1) | 156 | 47 (39-54 IQR) | 26 (TP4) | 60 | A: 76 (4-yr RFS) B: 58 (4-yr RFS) p = 0.028 | A: 79 (4 yr) B: 72 (4 yr) p = 0.88 |
| MDACC(US) NCT01424982 2011-2019 | No | 2 | PON + hyper-CVAD | 86 (66a) | 46 (21-80) | 87 (best) | 23 | 65 (6-yr EFS) 80 (6-yr DFS) | 75 (6 yr) |
| GIMEMA(Italy) INCB4344-20/ LAL1811 NCT01641107 2014-2017 | Yes | 2 | PON + pred | 44 | 67 (26-85); 80% ≥ 60 yrs | 41 (week 24) 82% (overall) | 14 | 14.3 mo (med, EFS) | NR (median) |
| PETHEMA(Spain) PONAFIL NCT02776605 2017-2020 | No | 2 | PON + high- int chemo | 30 | 49 (19-59) | 47 (ind) 71% (cons) | 87 | 70 (3-yr EFS) | 96 (3 yr) |
| PhALLCON (Global) NCT03589326 2018-2022 | Yes | 3 | PON vs IM + low-int chemo (2:1) | 245 | 54 | MR4.5 after C9 46 (PON) 26 (IM) | 31 (PON) 37 (IM) | Med EFS 29.0 Med EFS NR (HR 0.65, 95% CI 0.39-1.1) | Med OS NR Med OS NR (HR 0.76, 95% CI 0.38-1.52) |
In remission at enrollment.
alloHSCT, allogeneic hematopoietic stem cell transplant; Chemo, chemotherapy; CMR, complete molecular remission; cons, consolidation; CR, complete remission; DAS, dasatinib; dex, dexamethasone; DFS, disease-free survival; EFS, event-free survival; HR, hazard ratio; IM, imatinib; ind, induction; int, intensity; IQR, interquartile range; med, median; mo, month; MR, molecular response; MRD, measurable residual disease; NIL, nilotinib; NR, not reached; OS, overall survival; PON, ponatinib; pred, prednisone; SAKK (France, Belgium, and Switzerland); TP, timepoint; US, United States; vinc, vincristine; yr, year.