Novel approaches to Ph+ ALL in older adults: published and ongoing trials*
| Reference . | Regimen . | Phase . | N . | Line . | Age, y . | Regimen- related deaths . | Response . | Survival . |
|---|---|---|---|---|---|---|---|---|
| Rousselot et al (2016)35 EWALL PH-01 NCT028889777 | Dasatinib 140 mg daily + low-intensity CC | 2 | 71 | First | ≥55 | 4% (3/71) induction 12% (6/71) treatment-related mortality in CR | 96% CR 65% 3-log reduction in BCR-ABL | 27% (95% CI, 17-37) 5-year EFS 36% (95% CI, 25-47) 5-year OS 7 received HSCT 75% of relapses T315I |
| Ottmann et al (2018)36 EWALL PH-02 NCT028889777 | Nilotinib 400 mg twice daily + low-intensity CC | 2 | 79 | First | ≥55 | 1% (1/79) induction 11 died in CR (6 after HSCT) | 94.4% CR | 42% 4-year EFS 47% 4-year OS (61% transplanted, 39% nontransplanted) 24 received alloHSCT, 3 received autoHSCT |
| Vignetti et al (2007)38 GIMEMA LAL0101-B | Imatinib 800 mg daily + prednisone (induction protocol only) | 2 | 29 | First | >60 | 0% induction 2 died in CR | 100% CR 1/27 CMR | 48% (95% CI, 28-69) 1-year DFS 74% (95% CI, 54-94) 1-year OS |
| Foà et al (2011)39 GIMEMA LAL1205 | Dasatinib 70 mg twice daily + prednisone (induction protocol only) | 2 | 53 | First | ≥18 (22%> 60) | 0% induction | 100% CR 52.1% 3-log reduction in BCR-ABL by day 85 | 69% (95% 61-79) 20-month OS 51% (95% CI, 44-59) 20-month DFS |
| Martinelli et al (2017)40 GIMEMA LAL1811 NCT01641107 | Ponatinib 45 mg daily + prednisone (induction protocol only) | 2 | 42 | First | >60 or unfit | 0% induction 1 death in follow-up ponatinib | 95.5% CR 45% CMR at 24 weeks | 87.5% (95% CI, 76.5%-99.9%) 1-year OS |
| Luskin et al (2019)42 DFCI IST NCT03595917 | Dasatinib 140 + asciminib (dose escalation) (induction protocol only) | 1 | 8 | First | >50 | 0% induction | 100% CR | Not reported |
| Foà et al (2020)43 GIMEMA LAL2116 NCT02744768 | Dasatinib 140 + prednisone Blinatumomab consolidation | 2 | 63 | First | ≥18 (median 54) | 1.6% induction (1 patient) No regimen related deaths in CR | 95% CR | With median follow-up 18 months 95% (95% CI, 90-100) OS 88% (95% CI, 80-97) DFS |
| Wieduwilt et al (2018)41 NCTN/Alliance 10701 NCT01256398 | Dasatinib 140 + dexamethasone induction CC consolidation Allo- vs autoHSCT | 2 | 64 | First | ≥18 (median 60) | 0% induction deaths | 97% CR | 43% 3-year DFS (55% allo, 43% auto, 46% chemo) 55% 3-year OS (63% ≤ 60 years, 49%> 60 years) (75% allo, 71% auto, 55% chemo) Relapse 25% allo, 43% auto, 37% chemo |
| NCTN/EA9181 NCT04530565 | TKI + prednisone induction TKI + hyper-CVAD vs TKI + blinatumomab consolidation | 3 | — | First | ≥18-75 | Results pending | Results pending | Results pending |
| SWOG 1318 NCT02143414 | Dasatinib + prednisone induction Dasatinib + blinatumomab consolidation | 2 | — | First | ≥65 | Results pending | Results pending | Results pending |
| Reference . | Regimen . | Phase . | N . | Line . | Age, y . | Regimen- related deaths . | Response . | Survival . |
|---|---|---|---|---|---|---|---|---|
| Rousselot et al (2016)35 EWALL PH-01 NCT028889777 | Dasatinib 140 mg daily + low-intensity CC | 2 | 71 | First | ≥55 | 4% (3/71) induction 12% (6/71) treatment-related mortality in CR | 96% CR 65% 3-log reduction in BCR-ABL | 27% (95% CI, 17-37) 5-year EFS 36% (95% CI, 25-47) 5-year OS 7 received HSCT 75% of relapses T315I |
| Ottmann et al (2018)36 EWALL PH-02 NCT028889777 | Nilotinib 400 mg twice daily + low-intensity CC | 2 | 79 | First | ≥55 | 1% (1/79) induction 11 died in CR (6 after HSCT) | 94.4% CR | 42% 4-year EFS 47% 4-year OS (61% transplanted, 39% nontransplanted) 24 received alloHSCT, 3 received autoHSCT |
| Vignetti et al (2007)38 GIMEMA LAL0101-B | Imatinib 800 mg daily + prednisone (induction protocol only) | 2 | 29 | First | >60 | 0% induction 2 died in CR | 100% CR 1/27 CMR | 48% (95% CI, 28-69) 1-year DFS 74% (95% CI, 54-94) 1-year OS |
| Foà et al (2011)39 GIMEMA LAL1205 | Dasatinib 70 mg twice daily + prednisone (induction protocol only) | 2 | 53 | First | ≥18 (22%> 60) | 0% induction | 100% CR 52.1% 3-log reduction in BCR-ABL by day 85 | 69% (95% 61-79) 20-month OS 51% (95% CI, 44-59) 20-month DFS |
| Martinelli et al (2017)40 GIMEMA LAL1811 NCT01641107 | Ponatinib 45 mg daily + prednisone (induction protocol only) | 2 | 42 | First | >60 or unfit | 0% induction 1 death in follow-up ponatinib | 95.5% CR 45% CMR at 24 weeks | 87.5% (95% CI, 76.5%-99.9%) 1-year OS |
| Luskin et al (2019)42 DFCI IST NCT03595917 | Dasatinib 140 + asciminib (dose escalation) (induction protocol only) | 1 | 8 | First | >50 | 0% induction | 100% CR | Not reported |
| Foà et al (2020)43 GIMEMA LAL2116 NCT02744768 | Dasatinib 140 + prednisone Blinatumomab consolidation | 2 | 63 | First | ≥18 (median 54) | 1.6% induction (1 patient) No regimen related deaths in CR | 95% CR | With median follow-up 18 months 95% (95% CI, 90-100) OS 88% (95% CI, 80-97) DFS |
| Wieduwilt et al (2018)41 NCTN/Alliance 10701 NCT01256398 | Dasatinib 140 + dexamethasone induction CC consolidation Allo- vs autoHSCT | 2 | 64 | First | ≥18 (median 60) | 0% induction deaths | 97% CR | 43% 3-year DFS (55% allo, 43% auto, 46% chemo) 55% 3-year OS (63% ≤ 60 years, 49%> 60 years) (75% allo, 71% auto, 55% chemo) Relapse 25% allo, 43% auto, 37% chemo |
| NCTN/EA9181 NCT04530565 | TKI + prednisone induction TKI + hyper-CVAD vs TKI + blinatumomab consolidation | 3 | — | First | ≥18-75 | Results pending | Results pending | Results pending |
| SWOG 1318 NCT02143414 | Dasatinib + prednisone induction Dasatinib + blinatumomab consolidation | 2 | — | First | ≥65 | Results pending | Results pending | Results pending |
Results at most recent publication.
CMR, complete molecular response; DFS, disease-free survival; EFS, event-free survival.