PhALLCON: Impact of MRD negativity post induction with ponatinib vs imatinib in newly diagnosed Ph+ ALL

Ponatinib, a third-generation BCR::ABL1TKI, was approved by the FDA for the treatment of ND Ph+ ALL based on results from the PhALLCON trial (NCT03589326).¹ The ALL Hub previously reported the results from this trial. PhALLCON is a randomized, multicenter, open-label, phase III trial evaluating the efficacy and safety of ponatinib vs imatinib combined with RIC in adults with ND Ph+ ALL. Eligible patients were randomized 2:1 to receive ponatinib (n = 164) or imatinib (n = 81) in combination with RIC. 

A post hoc analysis from this trial evaluating the outcomes of ponatinib vs imatinib in patients who did not achieve MRD negativity by EOI was presented by Aldoss at the 2025 ASCO Annual Meeting.¹ This analysis included 113 patients who did not achieve MRD negativity (≤0.01% or better) by EOI and continued treatment. Outcomes included molecular response rates, RFS, OS, PFS, and safety.¹

Key learnings 

A higher MRD negativity (≤0.01% or better) was achieved at all time points with ponatinib vs imatinib 38% vs 28% (EOC9), 41% vs 30% (EOC20), and 48% vs 33% (EOT).

In the ponatinib vs imatinib arms, median DoR was NR vs 3.8 months, 2-year EFS was 87% vs 62%, 2-year OS was 91.3% vs 87.3%, median PFS was 8.5 months vs 7.3 months, and 2-year PFS was 36.3% vs 12.7%.

TEAEs in ponatinib vs imatinib arms were 100% vs 98% (Grade ≥3: 91% vs 94%); dose modification due to TEAEs was 71% vs 54% (discontinuation: 15% vs 9%; reduction: 16% vs 28%; interruption: 66% vs 41%).

These data strengthen the effectiveness and tolerability findings from the PhALLCON trial and support the use of ponatinib in combination with RIC for patients with ND Ph+ ALL without MRD negativity by EOI.