Table 1.

Summary of the ponatinib and imatinib studies included in the MAIC

Characteristic	MDACC [14]	GIMEMA LAL1811 [34]	GRAAPH-2005 [15]	NCT00038610 [11]	CSI57ADE10 [42]
Treatment	Ponatinib + hyper-CVAD	Ponatinib + steroids	Imatinib + reduced intensity chemotherapy or Imatinib + hyper-CVADa	Imatinib + hyper-CVAD	Imatinib monotherapy followed by age-adapted/intrathecal chemotherapy consolidation with imatinib
Study design	Single-center, open-label, single-arm, phase 2	Multicenter, open-label, single-arm, phase 2	Multicenter, randomized, open-label, two-arms, phase 3	Single-center, open-label, single-arm, phase 2	Multicenter, randomized, open-label, single-arm, phase 2
Population size	87	44	133b/268c	54	55
Intervention(s)	Oral ponatinib at a dose of 45 mg/day for the first 14 days of cycle 1, then daily dose of 45 mg/day for the next 7 cycles of consolidation therapy 8 cycles of 21 days, alternating between two drug combinations: hyper-CVAD and high-dose methotrexate + cytarabine Patients in complete remission received maintenance with ponatinib 45 mg/day with vincristine and prednisone monthly for 2 years followed by ponatinib for up to 3 years or indefinitely	Oral ponatinib at a dose of 45 mg/day for 6 weeks (defined as one course) for 8 courses Prednisone at 60 mg/m2/day from days 1 to 21; the dose was then tapered, and treatment was stopped at day 29	Induction with imatinib + reduced-intensity chemotherapy vs. induction with hyper-CVAD in cycle 1 Induction in cycle 1 followed by imatinib + methotrexate + cytarabine cycle 2 to bridge to stem cell transplantation Up to 8 cycles of treatment alternating imatinib + hyper-CVAD with imatinib + methotrexate + cytarabine for patients not receiving transplant	8 induction-consolidation courses of imatinib + hyper-CVAD alternated with imatinib + methotrexate + cytarabine	Imatinib induction followed by imatinib + age-adapted/intrathecal chemotherapy consolidation After pre-phase chemotherapy, patients were randomly assigned to imatinib at a dose of 600 mg/day or multi-agent induction chemotherapy in a 4-week cycle After completing remission therapy, patients randomized to either treatment arm (imatinib vs. chemotherapy) received imatinib at a dose of 600 mg/day imatinib + successive cycles of consolidation and reinduction chemotherapy
Primary endpoint	EFS	Proportion of patients with a CHR	MMolR rate after 2 years	Response to induction therapy with imatinib + hyper-CVAD (from baseline to 6 months), CR, PR, induction death, DFS	Rate of hematological remission after induction therapy
Other endpoints	ORR, OS, DFS, complete remission, partial remission, molecular response	Molecular response, cytogenetic response, duration of molecular response, duration of cytogenetic response, EFS, OS	EFS, RFS, CIR, cumulative incidence of NRM, OS	OS	OS, DFS, complete remission, molecular response
Median follow-up duration	45.1 months	34.9 months	4.8 years	130 months among surviving patients	11.2 months among surviving patients
Eligible for HDT-SCT	Yes	No	Yes	Yes	No
Comparator MDACC or GIMEMA LAL1811 population			MDACC patients < 60 years with active disease at baseline, not previously treated with TKIs	MDACC patients not previously treated with TKIs	GIMEMA LAL1811 patients > 54 years
Year of study completion	2021	Not reported	2014	2014	2006

CHR complete hematologic response, CIR cumulative incidence of relapse, CVAD cyclophosphamide, vincristine, doxorubicin, and dexamethasone, CR complete remission, DFS disease-free survival, EFS event-free survival, HDT-SCT, high-dose therapy and stem cell transplant, MAIC matching adjusted treatment comparison, MMolR major molecular response, NRM non-relapse-related mortality, ORR overall response rate, OS overall survival, PR partial remission, RFS relapse-free survival, TKI tyrosine kinase inhibitor

^aThe MAIC only used data for the imatinib + hyper-CVAD arm

^bNumber of patients treated with imatinib + hyper-CVAD

^cTotal number of patients in the study