Ponatinib in relapsed/refractory Ph+ ALL: Real-world outcomes

Results from a retrospective real-world analysis evaluating ponatinib monotherapy in 79 adults with relapsed/refractory (R/R) Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL), including those with measurable residual disease (MRD) relapse, were recently published in Acta Haematologica by Min et al.

Key data: Complete remission (CR) was achieved in 60.7% of patients (n = 48), with 47.8% of responders achieving complete molecular response (CMR). Ponatinib initiation at MRD relapse vs hematologic relapse was associated with improved molecular response. However, 2-year overall survival (OS) remained poor at 29.5% (95% confidence interval [CI], 18.9–40.9%). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed in 48.1% of patients (n = 38), with 2-year post-transplant OS of 29.1% (95% CI, 12.9–47.6%). Age <60 years and MRD response better than major molecular response (MMR) were linked to improved OS in multivariate analysis.

Key learning: Ponatinib monotherapy achieved acceptable CR and MRD response rates in patients with R/R Ph+ ALL, but long-term survival remained suboptimal despite subsequent allo-HSCT, supporting earlier intervention and the need for combination strategies to improve durability.