MD Anderson Cancer Center
Front-line and R/R ALL Treatment Regimens Hyper-CVAD + Rituximab in Precursor B-ALL
Intensive phase
1 2 2 3 3 4 4 5 5 6 7 8
Maintenance phase
11--55 66 7 8-178-17 1818 1919 12-2420-30
Hyper-CVAD Rituximab POMP MTX-ara-C IT MTX, ara-C MTX-asp
Thomas. JCO 2010; 28:3880-9 HCVAD + Ofatumumab in B-ALL : Design
Intensive phase
1 2 2 3 3 4 4 5 5 6 7 8
Maintenance phase
11--55 66 7 8-178-17 1818 1919 12-2420-30
Hyper-CVAD Ofatumumab POMP MTX-ara-C IT MTX, ara-C MTX-Peg asp
Richard-Carpentier. Blood 134 : Abst 2577; 2019 Hyper-CVAD + Blinatumomab in B-ALL (Ph-negative B- ALL < 60 years). Treatment schedule Intensive phase Blinatumomab phase *After 2 cycles of chemo for Ho-Tr, Ph-like, t(4;11)
1 2 3 4 1 2 3 4
4 wk 2 wk
Maintenance phase
1-3 4 5-7 8 9-11 12 13-15
Hyper-CVAD Ofatumumab or Rituximab MTX-Ara-C 8 x IT MTX, Ara-C POMP Blinatumomab Richard-Carpentier. Blood 134: abst 3807; 2019 Hyper-CVAD + Inotuzmab + Blinatumomab in B-ALL (Ph- negative B-ALL < 60 years) Intensive phase Blinatumomab phase *After 2 cycles of chemo for Ho-Tr, Ph-like, t(4;11)
1 2 3 4 1 2 3 4
4 wk 2 wk Maintenance phase 1-3 4 5-7 8 9-11 12 13-15
Hyper-CVAD Rituximab or Ofatumumab MTX-Ara-C IT MTX, Ara-C POMP Blinatumomab Inotuzumab 0.3 mg/m2 on D1 and D8 Mini-HCVD + INO ± Blina in Older ALL: Modified Design (Pts #50+)
Intensive phase Mini-HCVD Blinatumomab Mini-MTX-cytarabine 1 2 3 4 POMP IT MTX, Ara-C
INO* Total dose Dose per day Consolidation phase (mg/m2) (mg/m2) C1 0.9 0.6 D2, 0.3 D8 5 6 7 8 C2-4 0.6 0.3 D2 and D8 Total INO dose = 2.7 mg/m 2 Maintenance phase *Ursodiol 300mg tid for 1-3 4 5-7 8 9-11 12 13-15 16 VOD prophylaxis 18 months Jabbour E et al. Cancer 2018;124(20):4044-55; Kantarjian. Lancet Oncology 19:240; 2018 Mini-HCVD + INO ± Blina in Older ALL: Amended Design (Pts ≥70 years)
Intensive phase Mini-HCVD Blinatumomab Mini-MTX-cytarabine 1 2 POMP IT MTX, Ara-C
INO* Total dose Dose per day Consolidation phase (mg/m2) (mg/m2) C1 0.9 0.6 D2, 0.3 D8 5 6 7 8 C2 0.6 0.3 D2 and D8 Total INO dose = 1.5 mg/m 2 Maintenance phase *Ursodiol 300mg tid for VOD prophylaxis 1 2 3 4 6 months Hyper-CVAD + Ponatinib. Design Intensive phase 45 30/15 1 2 3 4 5 6 7 8 Maintenance phase 30/15 30/15
24 months 12 intrathecal CNS prophylaxis Hyper-CVAD Ponatinib 45 mg →30 mg →15 mg MTX-cytarabine Vincristine + prednisone
• After the emergence of vascular toxicity, protocol was amended: Beyond induction, ponatinib 30 mg daily, then 15 mg daily once in CMR Jabbour. Lancet Onc. 16:1547;2015. Jabbour. Lancet Hematology 5: 618; 2018 Blinatumomab-ponatinib in Ph-Positive ALL
Induction phase Consolidation phase: C2-C5
30 mg 15 mg in CMR
1 2
4 wk 2 wk 4 wk 2 wk
Maintenance phase 15 mg for 5 years
Blinatumomab IT MTX, Ara-C Ponatinib 30 mg Ponatinib 15 mg
Assi. Clin Lymphoma Myeloma Leuk. 2017;17(12):897-901 Hyper-CVD + Ponatinib + Blinatumomab in Ph- positive ALL Intensive phase 30 30/15 1 2 3 4 1 2 3 4
4 wk 2 wk Maintenance phase 30/15 30/15
4 8 12
16 months 5 years CNS prophylaxis (N=12)
Mini-Hyper-CVD Ponatinib 30 mg →15 mg Mini-MTX-cytarabine Vincristine + prednisone Blinatumomab Mini-HCVD + INO ± Blinatumomab in R/R ALL Modified Design
Intensive phase Mini-HCVD Blinatumomab Mini-MTX-cytarabine 1 2 3 4 POMP IT MTX, Ara-C
INO Total dose Dose per day Consolidation phase (mg/m2) (mg/m2) 5 6 7 8 C1 0.9 0.6 D1, 0.3 D8 C2-4 0.6 0.3 D1 and D8 Total INO dose = 2.7 mg/m2 Maintenance phase 1-3 4 5-7 8 9-11 12 13-15 16 18 months Jabbour. JAMA Oncology 4:230; 2018 Jabbour. Cancer. 2018 Oct 11. Sasaki. Blood. 132: abst 553; 2018 Hyper-CVD + Blinatumomab in R-R B-ALL Induction phase Consolidation phase: C2-C4
1A 1B 2A 2B 3A 3B 4A 4B
1 2 3 4
4 wk 2 wk 4 wk 2 wk 4 wk 2 wk 4 wk 2 wk Maintenance phase
M6 M12
12 months 12 months Hyper-CVD Rituximab (n=8) Blinatumomab MTX-Ara-C IT MTX, Ara-C (n=8) POMP VCR/Steroid Hyper-CVD + Venetoclax for R-R and FL Elderly ALL
CR/CRi by cycle 2:
BM assessment for for assessment BM Complete 8 total cycles of Cycle 1 (28d) hyper-CVD + venetoclax, then 2 response Venetoclax (days 1-14), years of maintenance (or HSCT) R/R Ph-negative ALL Hyper-CVD (days 1-4)
FL elderly ALL Cycle 2 (28d) Venetoclax (days 1-7), No response by cycle 2: MTX/Ara-C (days 1-4) Off study
• Patients with T-ALL also receive nelarabine + peg-asparaginase • Maintenance x 2 years with vincristine + prednisone + venetoclax