Efficacy of Ponatinib Versus Earlier Generation Tyrosine Kinase Inhibitors for Front-line Treatment of Newly Diagnosed Philadelphia-positive Acute Lymphoblastic Leukemia

Abstract

Introduction: Complete molecular response (CMR) and 2- and 3-year overall survival (OS) were compared for patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph⁺ ALL) who had undergone front-line combination chemotherapy plus ponatinib versus combination therapy plus earlier generation tyrosine kinase inhibitors (TKIs; imatinib, dasatinib, and nilotinib).

Patients and methods: We identified 26 Ph⁺ ALL studies: 25 of earlier generation TKIs and 1 of ponatinib. The outcomes from studies of combination chemotherapy plus earlier generation TKIs were summarized using pooled estimates with 95% confidence intervals (CIs) from a random-effects meta-analysis. A binomial distribution was assumed to calculate the 95% CIs for the results from the single-arm combination chemotherapy plus ponatinib trial. Adjusted logistic meta-regression analyses were used to compare the outcomes between the TKI groups.

Results: The percentage of patients achieving a CMR was greater with combination chemotherapy plus ponatinib (79%) than the pooled percentage of patients achieving a CMR with combination chemotherapy plus earlier generation TKIs (34%). Greater OS was observed with ponatinib compared with the pooled OS for earlier generation TKIs (2-year, 83% vs. 58%; 3-year, 79% vs. 50%). Odds ratios for ponatinib versus earlier generation TKIs were 6.09 (95% CI, 1.16-31.90; P = .034) for CMR, 3.70 (95% CI, 0.93-14.73; P = .062) for 2-year OS, and 4.49 (95% CI, 1.00-20.13; P = .050) for 3-year OS.

Conclusion: Ponatinib plus chemotherapy might be associated with better outcomes than chemotherapy with earlier generation TKIs in patients with newly diagnosed Ph⁺ ALL.

Keywords: Combination therapy; Complete molecular response; Meta-analysis; Meta-regression; Overall survival.