Dasatinib for acute lymphoblastic leukemia

Abstract

Introduction: Despite considerable improvement in the prognosis of Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in the era of tyrosine-kinase inhibitors (TKI), less than half of the patients can be cured. Among several TKI now available, dasatinib (SPRYCEL®) displays theoretical advantages and a robust clinical experience.Areas covered: After an overview of Ph+ ALL current and future therapies, this article presents the chemistry, pharmacodynamics and pharmacokinetics of dasatinib, shedding light on mechanisms of action, resistance and toxicity. Clinical efficacy and tolerability of the drug, alone or in combination with chemotherapy and/or hematopoietic stem cell transplantation, are detailed in phase I and II trials, and in one phase III trial dedicated to dose optimization, in the absence of direct comparative studies between various TKI. A potential role for dasatinib in other subsets of ALL is discussed.Expert opinion: Dasatinib displays an interesting tolerance/efficacy profile in ALL; rates of hematologic and molecular remission of 90% and 35% respectively; disease-free survival at 3 years of 25% to 70% and rare cardio-vascular events; its drawbacks include pleural effusions, risk of hemorrhage and the selection of resistant clones. The main competitors are represented by other drugs targeting the BCR-ABL kinase, such as ponatinib and allosteric inhibitors, and by the growing field of immunotherapy.