ABSTRACT
Despite the notion that the expected survival for most, but not all, patients with chronic myeloid leukemia (CML) now approaches that of the general population, much depends on achieving an optimal response and of course monitoring the patients for response and adverse events appropriately. It is therefore important to continue our efforts in offering patients access to good practice clinical trials that address the issues of optimizing care and potential long-term remissions and probable cure, with the possibility to discontinue the treatments safely. In this chapter, recent efforts in immunotherapy and some of the novel drugs, such as ponatinib, which might offer the potential to improve upon the second-generation tyrosine kinase inhibitors (TKIs), in terms of both effi cacy and safety are discussed.
PONATINIB Ponatinib (formerly called AP24534, Ariad Pharmaceuticals, Cambridge, Massachusetts, USA) is a rationally designed oral inhibitor of BCR-ABL1 that binds both active and inactive conformations of the enzyme and is active against a broad array of BCR-ABL1 mutants, including T315I. It has an interesting chemical structure based on a purine scaffold and a central triple carbon-carbon bond with a substructure that is similar to imatinib. The drug inhibits ABL, SRC and a variety of other kinases. Results from the phase I study of this agent, presented in December 2010, which included 32 evaluable patients with CML in chronic phase, demonstrated that 30 (94%) had complete hematologic response (CHR), and 20 (63%) had major cytogenetic response (MCyR): 12 CCyR and eight partial CyR. Remarkably, of 20 CML-chronic-phase cytogenetic responders, 18 remain on treatment [mean duration 326 (range 142-599) days] without progression. There were 11 CML-chronic-phase
