STUDY DESIGN

Ponatinib is a third-generation BCR::ABL tyrosine kinase inhibitor (TKI) that inhibits BCR::ABL1 regardless of any single resistance mutations, including T315I.¹ It was previously evaluated in the PhALLCON (ponatinib-3001) trial in adults with newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).¹ The trial met its primary endpoint with a significantly higher rate of minimum residual disease (MRD)-negative complete remission (CR) at the end of induction (EOI) with ponatinib, compared with imatinib (34.4% vs. 16.7%; p=0.002).¹

PhALLCON is a global, phase 3, randomized, open-label, multicenter trial conducted to compare the efficacy and safety of ponatinib and imatinib in newly diagnosed Ph+ ALL.¹ A total of 245 eligible patients were randomized 2:1 to receive ponatinib starting dose of 30mg once daily (QD) (n=164) or imatinib 600mg QD (n=81) in combination with 20 cycles of reduced-intensity chemotherapy.¹ In the ponatinib arm, a dose reduction to 15mg QD was offered when MRD-negative CR was achieved after the EOI.¹

The captioned post-hoc subgroup analysis of PhALLCON evaluated the rates of MRD negativity and progression-free survival (PFS) in randomized patients with p190/p120 BCR::ABL1 variants confirmed by a central laboratory (ponatinib n=154; imatinib n=78) over a median trial period of 20.1 months.¹ These efficacy outcomes were stratified by age (<65 and ≥65 years), and BCR::ABL1 variant subgroups (p190 and p210).¹ MRD negativity was defined as BRC::ABL1^IS ≤0.01%.¹ PFS events included any-cause death, failure to achieve CR by EOI, relapse from CR, and failure to achieve or loss of MRD negativity.¹ Outcomes in patients who proceeded to hematopoietic stem cell transplantation (HSCT) were also explored.¹ TEAEs, including arterial occlusive events (AOEs) and venous thromboembolic events (VTEs), were evaluated in all patients and those without HSCT.¹
 

FINDINGS