Investigating the efficacy and safety of ponatinib in acute lymphoblastic leukemia: A systematic review.

Abstract

e18531 Background: Ponatinib has been well studied in treating Chronic Myeloid Leukemia. However, there are no reviews to date analyzing the efficacy of ponatinib in treating Ph+ Acute Lymphoblastic Leukemia (ALL). Ponatinib is a 3rd generation, broad-spectrum tyrosine kinase inhibitor (TKI) designed to suppress mutations conferring resistance to earlier generations of TKIs including the threonine to isoleucine mutation at position 315 (T315I) in the BCR-ABL fusion protein. We aim to review clinical studies evaluating the efficacy of ponatinib in Ph+ ALL populations. Methods: PubMed, Embase, and the Cochrane Library were screened for published, peer-reviewed clinical studies. Study variables included patient age, BCR-ABL T315I mutation status, previous TKI therapy, comorbidities, dosage, median duration of therapy, median follow-up, the use of combination therapy, response and overall survival, and adverse events. To evaluate efficacy, we compared hematologic, cytogenetic, and molecular response rates as well as overall survival and progression-free survival. Results: From 1088 identified studies, 14 clinical studies were included. Two studies illustrated ponatinib as a promising treatment for Ph+ ALL alone, 4 studies indicated that ponatinib is more effective when coupled with chemotherapy, and 5 studies illustrated superior overall survival (OS) rates of ponatinib compared to 1st and 2nd generation TKIs. In particular, the average 3-year OS rates of ponatinib compared to imatinib was 98% vs 58% respectively; the average 3-year OS of ponatinib vs dasatinib was 87.5% vs 46.5% respectively. Out of 583 individuals, there were 56 reports of adverse dermatologic events, 80 adverse events affecting the gastrointestinal tract, and 141 affecting the circulatory system. Out of 56 Ph+ ALL patients carrying the T315I mutation, 52 experienced anti-leukemic responses. Conclusions: Ponatinib exhibits promising response rates for Ph+ ALL patients, especially when combined with chemotherapy and allo-SCT, as well as superior overall survival rates compared to earlier generation TKIs.