Michele Baccarani discusses the factors influencing the decision to switch tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukaemia and the options available for patients who develop the T315I "gatekeeper" mutation.
Disclosures: Michele Baccarani has received honoraria from ARIAD, BMS, Novartis and Pfizer for consultancies and speaker fees.
FILMED AT THE EUROPEAN HEMATOLOGY ASSOCIATION (EHA) ANNUAL MEETING, JUNE 2016
WHAT FACTORS INFLUENCE THE DECISION TO SWITCH TYROSINE KINASE INHIBITOR (TKI) THERAPY IN CHRONIC MYELOID LEUKAEMIA (CML)?
00:13 – Many facts. Facts concerning toxicity side effects or adverse events and as this case, the switch to another TKI is due, is necessary. But we can switch to another TKI also to increase efficacy. And we can have an early switch or a late switch. Early switch means that after three months if the response, if the molecular response is non-optimal, we can switch to a second generation TKI so as to increase the probability of achieving a deeper molecular response later on. Late switch is different. Late switch means that we have a patient who is well, alive, he will have a normal survival, but he or she is not able to reach a deeper molecular response that is necessary to achieve treatment for remission. And as that case there are studies investigating if late switch to a second generation TKI may increase the number of patients with deeper molecular response, so may increase the probability of tuning treatment for remissions. This is a fairly good expectation, but still, it is an expectation.
WHAT ARE THE OPTIONS FOR PATIENTS WHO DEVELOP THE T315I “GATEKEEPER” MUTATION?
01:31 – Today, there is only one option, that is the so called third or second generation TKI called ponatinib. This is the only option for these patients. There are other TKI in development but still, this is the unique TKI available, regrettably not worldwide. So ponatinib is the drug of choice for patients with these kind of mutations. Today, nobody knows whether these patients should continue on ponatinib or should be moved to stem-cell transplantation.
WHAT PROMISING THERAPEUTIC OPTIONS ARE IN CLINICAL DEVELOPMENT?
02:11 – Many, but we do not know how many will be successful. Probably the most important is the combination of different TKIs and the most promising is a combination of second generation TKI called nilotinib with a fourth generation TKI that is called ABL001, because maybe this kind of combination, ABL001 is an allosteric inhibitor. So it has a mechanism of action completely different. And maybe combined this TKI, it’s maybe possible to get free of any leukemic cells. But let me also have a dream. This is a dream in five years or 10 years from now, that the combination of TKI with the so called PD-1 inhibitors, the checkpoint inhibitors may probably, has the potential to cure chronic myeloid leukaemia patients.