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.

Keywords:

• dasatinib
• chronic myeloid leukemia in lymphoid blast crisis
• Philadelphia-chromosome positive acute lymphoblastic leukemia
• tyrosine-kinase inhibitors

Declaration of interests

The author has received honoraria from ARIAD, Bristol-Myers Squibb, Novartis, Pfizer and Amgen. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Notes on contributors

Françoise Huguet

Affiliation

Françoise Huguet^†

^†Author for correspondence

E-mail: [email protected]

Hematology Department, Institut Universitaire du Cancer Toulouse-Oncopole, 1 avenue Irène Joliot-Curie,Toulouse 31400,France