AYA treatment regimens
| . | ALL-96 (PETHEMA)29 . | DFCI Adult ALL 01-17532 . | C1040334 . |
|---|---|---|---|
| Patient population | |||
| Number of patients | 81 | 92 | 318 |
| Median age at diagnosis (range) | 20 years (15-30) | 28 years (18-50) | 24 years (17-39) |
| Gender | Male: 62% | Male: 61% | Male: 61% |
| Immunophenotype | Precursor B- and T-cell ALL | Precursor B cell (80%) and precursor T cell (20%) | Precursor B cell (76%) and precursor T cell (24%) |
| Regimen | |||
| Induction | Vincristine: 2 mg IV (d 1, 8, 15, 22) Daunorubicin: 30 mg/m2 IV (d 1, 8, 15, 22) Prednisone: 60 mg/m2 (d 1-27), 30 mg/m2 (d 28-35) PO/IV Asparaginase: 10 000 U/m2 IV, (d 10-12, 17-19, 24-26) Cyclophosphamide: 1000 mg/m2 (d 36) | Vincristine: 2 mg IV (d 1, 8, 15, 22) Doxorubicin: 30 mg/m2 IV (d 1, 2) Prednisone: 40 mg/m2 PO (d 1-28) Methotrexate: 4 g/m2 IV (d 3, 8 to 24 h after doxorubicin) E colil-asparaginase 25 000 IU/m2 IM (d 5) Followed by CNS therapy (see below) | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 8, 15, 22) Daunorubicin: 25 mg/m2 IV (d 1, 8, 15, 22) Prednisone: 60 mg/m2 IV/PO (d 1-28) PEG-asparaginase: 2500 IU/m2 IM/IV (d 4) Extended remission induction (2 wk) administered if failure to achieve morphologic remission on d 29 bone marrow biopsy |
| Consolidation-1/ intensification | Mercaptopurine: 50 mg/m2 PO (d 1-7) | Vincristine: 2 mg (d 1) | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 15, 22, 43, 50) |
| Methotrexate: 3 g/m2 IV (d 1, 28, 56) | Methotrexate: 30 m/m2 IV/IM weekly | Cyclophosphamide: 1000 mg/m2 (d 1, 29) | |
| VM-26: 150 mg/m2 IV (d 14, 42) | Dexamethasone: 18 mg/m2 PO (d 1-5) | Cytarabine: 75 mg/m2 IV/SC (d 1-4, 8-11, 29-32, 36-39) | |
| Cytarabine: 500 mg/m2 IV (d 14-15, 42, 43) | Mercaptopurine: 50 mg/m2 PO (d 1-14) | Mercaptopurine: 60 mg/m2 PO (d 1-14, 29-42) | |
| E coli asparaginase: 12 500 IU/m2 starting dose | PEG-asp: 2500 IU/m2 IM/IV (d 15, 43) | ||
| Doxorubicin: 30 mg/m2 IV (d 1) | |||
| Consolidation-2/interim maintenance | Dexamethasone: 10 mg/m2 (d 1-14), 5 mg/m2 (d 15-21) PO/IV Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 8, 15) Daunorubicin: 30 mg/m2 IV (d 1, 2, 8, 9) Cyclophosphamide: 600 mg/m2 (d 1, 15) Asparaginase: 10 000 U/m2 IV, (d 1-3, 15-17) | N/A | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 11, 21, 31, 41) Methotrexate: 100 m/m2 IV starting, with dose escalation (d 1, 11, 21, 31, 41) PEG-asp: 2500 IU/m2 IM/IV (d 2, 22) |
| Delayed intensification | N/A | N/A | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 8, 15, 43, 50) |
| Dexamethasone: 10 mg/m2 PO/IV (d 1-7, 15-21) | |||
| Doxorubicin: 25 mg/m2 IV (d 1, 8, 15) | |||
| PEG-asp: 2500 IU/m2 IM/IV (d 4, 43) | |||
| Cyclophosphamide: 1000 mg/m2 (d 29) | |||
| Cytarabine: 75 mg/m2 IV/SC (d 29-32, 36-39) | |||
| Thioguanine (6-TG): 60 mg/m2 PO (d 29-42) | |||
| Maintenance/continuation | Maintenance-1 (until wk 52) Methotrexate IM: 20 mg/m2 per wk Mercaptopurine: PO 50 mg/m2 daily Reinduction (every 4 wk) Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1) Prednisone: 60 mg/m2 daily Asparaginase: 20 000 U/m2 IV (d 1) Maintenance-2 (wks 53-104) Methotrexate IM: 20 mg/m2 per wk Mercaptopurine PO: 50 mg/m2 daily | Cycles every 3 wk × 74 wk Vincristine: 2 mg (d 1) Methotrexate: 30 mg/m2 IV/IM weekly Dexamethasone: 6 mg/m2 PO (d 1-5) Mercaptopurine: 50 mg/m2 PO (d 1-14) Doxorubicin: 30 mg/m2 IV (d 1) | Duration: Females 2 y, males 3 y (12-wk courses) Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 29, 57) Dexamethasone: 6 mg/m2 PO/IV (d 1-5, 29-33, 57-61) Mercaptopurine: 75 mg/m2 PO (d 1-84) Methotrexate: 20 mg/m2 PO weekly (d 8-78) – held on d 29 during 1st 4 courses (when IT methotrexate given) |
| CNS prophylaxis | Induction/Consolidation (d 1, 29) Methotrexate: 15 mg IT Cytarabine: 30 mg IT Hydrocortisone: 20 mg IT Maintenance/reinduction (d 1) Methotrexate: 15 mg IT Cytarabine: 30 mg IT Hydrocortisone: 20 mg IT | Induction Cytarabine: 50 mg IT (d 0) Cytarabine: 40 mg /methotrexate 12 mg/ hydrocortisone 50 mg IT (d 15 and 29) CNS therapy (3 wk) Vincristine: 2 mg IV (d 1) Mercaptopurine: 50 mg/m2 PO × 14 d Doxorubicin: 30 mg/m2 IV × 1 dose IT methotrexate/cytarabine twice weekly × 4 doses Cranial radiation (18-24 Gy) Intensification (30 wk) and continuation (74 wk) IT methotrexate/cytarabine/hydrocortisone at start of cycle | Induction Methotrexate: 15 mg IT (d 8, 29) Cytarabine: 70 mg IT (d 1) Consolidation Methotrexate: 15 mg IT (d 1, 8, 15, 22) Interim maintenance Methotrexate: 15 mg IT (d 1, 31) Delayed intensification Methotrexate: 15 mg IT (d 1, 29, 36) Maintenance Methotrexate: 15 mg IT (d 1), also given d 29 for first 4 courses |
| Outcomes | |||
| EFS | 61% (6-y) | 58% (4-y) | 66% (2-y) |
| OS | 69% (6-y) | 67% (4-y) | 78% (2-y) |
| . | ALL-96 (PETHEMA)29 . | DFCI Adult ALL 01-17532 . | C1040334 . |
|---|---|---|---|
| Patient population | |||
| Number of patients | 81 | 92 | 318 |
| Median age at diagnosis (range) | 20 years (15-30) | 28 years (18-50) | 24 years (17-39) |
| Gender | Male: 62% | Male: 61% | Male: 61% |
| Immunophenotype | Precursor B- and T-cell ALL | Precursor B cell (80%) and precursor T cell (20%) | Precursor B cell (76%) and precursor T cell (24%) |
| Regimen | |||
| Induction | Vincristine: 2 mg IV (d 1, 8, 15, 22) Daunorubicin: 30 mg/m2 IV (d 1, 8, 15, 22) Prednisone: 60 mg/m2 (d 1-27), 30 mg/m2 (d 28-35) PO/IV Asparaginase: 10 000 U/m2 IV, (d 10-12, 17-19, 24-26) Cyclophosphamide: 1000 mg/m2 (d 36) | Vincristine: 2 mg IV (d 1, 8, 15, 22) Doxorubicin: 30 mg/m2 IV (d 1, 2) Prednisone: 40 mg/m2 PO (d 1-28) Methotrexate: 4 g/m2 IV (d 3, 8 to 24 h after doxorubicin) E colil-asparaginase 25 000 IU/m2 IM (d 5) Followed by CNS therapy (see below) | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 8, 15, 22) Daunorubicin: 25 mg/m2 IV (d 1, 8, 15, 22) Prednisone: 60 mg/m2 IV/PO (d 1-28) PEG-asparaginase: 2500 IU/m2 IM/IV (d 4) Extended remission induction (2 wk) administered if failure to achieve morphologic remission on d 29 bone marrow biopsy |
| Consolidation-1/ intensification | Mercaptopurine: 50 mg/m2 PO (d 1-7) | Vincristine: 2 mg (d 1) | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 15, 22, 43, 50) |
| Methotrexate: 3 g/m2 IV (d 1, 28, 56) | Methotrexate: 30 m/m2 IV/IM weekly | Cyclophosphamide: 1000 mg/m2 (d 1, 29) | |
| VM-26: 150 mg/m2 IV (d 14, 42) | Dexamethasone: 18 mg/m2 PO (d 1-5) | Cytarabine: 75 mg/m2 IV/SC (d 1-4, 8-11, 29-32, 36-39) | |
| Cytarabine: 500 mg/m2 IV (d 14-15, 42, 43) | Mercaptopurine: 50 mg/m2 PO (d 1-14) | Mercaptopurine: 60 mg/m2 PO (d 1-14, 29-42) | |
| E coli asparaginase: 12 500 IU/m2 starting dose | PEG-asp: 2500 IU/m2 IM/IV (d 15, 43) | ||
| Doxorubicin: 30 mg/m2 IV (d 1) | |||
| Consolidation-2/interim maintenance | Dexamethasone: 10 mg/m2 (d 1-14), 5 mg/m2 (d 15-21) PO/IV Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 8, 15) Daunorubicin: 30 mg/m2 IV (d 1, 2, 8, 9) Cyclophosphamide: 600 mg/m2 (d 1, 15) Asparaginase: 10 000 U/m2 IV, (d 1-3, 15-17) | N/A | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 11, 21, 31, 41) Methotrexate: 100 m/m2 IV starting, with dose escalation (d 1, 11, 21, 31, 41) PEG-asp: 2500 IU/m2 IM/IV (d 2, 22) |
| Delayed intensification | N/A | N/A | Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 8, 15, 43, 50) |
| Dexamethasone: 10 mg/m2 PO/IV (d 1-7, 15-21) | |||
| Doxorubicin: 25 mg/m2 IV (d 1, 8, 15) | |||
| PEG-asp: 2500 IU/m2 IM/IV (d 4, 43) | |||
| Cyclophosphamide: 1000 mg/m2 (d 29) | |||
| Cytarabine: 75 mg/m2 IV/SC (d 29-32, 36-39) | |||
| Thioguanine (6-TG): 60 mg/m2 PO (d 29-42) | |||
| Maintenance/continuation | Maintenance-1 (until wk 52) Methotrexate IM: 20 mg/m2 per wk Mercaptopurine: PO 50 mg/m2 daily Reinduction (every 4 wk) Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1) Prednisone: 60 mg/m2 daily Asparaginase: 20 000 U/m2 IV (d 1) Maintenance-2 (wks 53-104) Methotrexate IM: 20 mg/m2 per wk Mercaptopurine PO: 50 mg/m2 daily | Cycles every 3 wk × 74 wk Vincristine: 2 mg (d 1) Methotrexate: 30 mg/m2 IV/IM weekly Dexamethasone: 6 mg/m2 PO (d 1-5) Mercaptopurine: 50 mg/m2 PO (d 1-14) Doxorubicin: 30 mg/m2 IV (d 1) | Duration: Females 2 y, males 3 y (12-wk courses) Vincristine: 1.5 mg/m2 - maximum 2 mg IV (d 1, 29, 57) Dexamethasone: 6 mg/m2 PO/IV (d 1-5, 29-33, 57-61) Mercaptopurine: 75 mg/m2 PO (d 1-84) Methotrexate: 20 mg/m2 PO weekly (d 8-78) – held on d 29 during 1st 4 courses (when IT methotrexate given) |
| CNS prophylaxis | Induction/Consolidation (d 1, 29) Methotrexate: 15 mg IT Cytarabine: 30 mg IT Hydrocortisone: 20 mg IT Maintenance/reinduction (d 1) Methotrexate: 15 mg IT Cytarabine: 30 mg IT Hydrocortisone: 20 mg IT | Induction Cytarabine: 50 mg IT (d 0) Cytarabine: 40 mg /methotrexate 12 mg/ hydrocortisone 50 mg IT (d 15 and 29) CNS therapy (3 wk) Vincristine: 2 mg IV (d 1) Mercaptopurine: 50 mg/m2 PO × 14 d Doxorubicin: 30 mg/m2 IV × 1 dose IT methotrexate/cytarabine twice weekly × 4 doses Cranial radiation (18-24 Gy) Intensification (30 wk) and continuation (74 wk) IT methotrexate/cytarabine/hydrocortisone at start of cycle | Induction Methotrexate: 15 mg IT (d 8, 29) Cytarabine: 70 mg IT (d 1) Consolidation Methotrexate: 15 mg IT (d 1, 8, 15, 22) Interim maintenance Methotrexate: 15 mg IT (d 1, 31) Delayed intensification Methotrexate: 15 mg IT (d 1, 29, 36) Maintenance Methotrexate: 15 mg IT (d 1), also given d 29 for first 4 courses |
| Outcomes | |||
| EFS | 61% (6-y) | 58% (4-y) | 66% (2-y) |
| OS | 69% (6-y) | 67% (4-y) | 78% (2-y) |
CCR, continuous complete remission; d, day; E coli, Escherichia coli; IM, intramuscular; IT, intrathecal; PO, by mouth; SC, subcutaneous; wk, weeks; y, years.