From the Journals

Ponatinib bests older TKIs against Ph+ALL


Key clinical point: Ponatinib may be more effective than first- or second-generation TKIs against Philadelphia chromosome-positive ALL.

Major finding: Complete molecular response rates and 3-year overall survival were better with ponatinib in combination with chemotherapy.

Study details: Meta-regression analysis of 26 studies of TKIs in combination with chemotherapy as first-line therapy for patients with Ph+ALL.

Disclosures: Ariad Pharmaceuticals funded the study. Dr. Jabbour and three coauthors reported research funding from the company; other study authors reported employment or other financial relationships with Ariad or its parent company, Takeda.

Source: Jabbour E et al. Clin Lymphoma Myeloma Leuk. 2018 18(4):257-65.



Every generation aspires to be better than its predecessors, and for the third-generation tyrosine kinase inhibitor ponatinib (Iclusig), that might just be true, investigators claim.

A retrospective analysis comparing clinical trial outcomes for patients with newly diagnosed acute lymphoblastic leukemia positive for the Philadelphia chromosome (Ph+ALL) suggests that first-line ponatinib offers modestly better complete molecular response (CMR) rates and 3-year overall survival (OS) than either first-generation TKIs such as imatinib (Gleevec) or second-generation agents such as dasatinib (Sprycel) and nilotinib (Tasigna).

“Although only 1 relevant study of ponatinib combined with chemotherapy in Ph+ALL has been reported and our ability to adjust for baseline patient characteristics was limited, the results suggest that ponatinib combined with chemotherapy might represent a more effective front-line treatment option than chemotherapy combined with an earlier generation TKI for patients with newly diagnosed Ph+ALL, including those who cannot or choose not to undergo [stem cell transplant],” wrote Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues.

They based their conclusions on a meta-regression analysis of 25 studies looking at first- or second-generation TKIs and one study of ponatinib as frontline therapy for patients with Ph+ALL. They described their results in Clinical Lymphoma, Myeloma & Leukemia.

The investigators created pooled estimates of outcomes from studies of earlier-generation TKIs plus combination chemotherapy using a random-effects meta-analysis method. For the sole ponatinib study – a single-arm trial of combination chemotherapy plus ponatinib – they used a binomial distribution method to calculate 95% confidence intervals (CI). The method essentially estimates the probability of success or failure of a repeated experiment.

They found that 79% of patients in the ponatinib trial achieved a CMR, compared with 34% of patients treated with earlier generation TKIs plus chemotherapy. This translates into an odds ratio (OR) for CMR with ponatinib of 6.09 (P = .034).

Two-year OS rates were 83% with ponatinib versus 58% for all patients treated with other TKIs. Although the OR (3.70) seemed to run in favor of ponatinib, the difference was not statistically significant (P = .062).

Next Article: