GIUSEPPE SAGLIO (TURIN)
FIRST LINE TKIs
Department of Clinical and Biological Sciences, University of Turin, Italy
Imatinib has been the first TKI (Tyrosin-Kinase-Inhibitor) of BCR-ABL1 introduced in the
therapy of CML (Chronic Myelogenous Leukemia) and has profoundly changed the outcome
perspectives of a disease previously fatal in the vast majority of the patients and that now
shows an overall survival similar to that of a control population without leukemia. However,
in addition to those who cannot tolerate the drug (approximately 10-15% of the total), 20-
25% of the imatinib patients treated with the usual dosage of 400 mg do not reach an optimal
response criteria according to the ELN (European Leukemia Net) recommendations. This has
led to explore as front-line therapy for CML second-generation tyrosine-kinase inhibitors like
nilotinib, dasatinib and bosutinib, more powerful TKIs with respect to imatinib and initially
registered as second line therapy for the CML cases intolerant or resistant to imatinib. The
clinical trials comparing imatinib versus the second generation TKIs have shown that the latter
are able to induce faster and deeper molecular responses with respect to 400 mg imatinib,
but that these advantages are counterbalanced by a higher degree of immediate and long-term
toxicities and by no improvement in the overall survival (OS) and progression free
survival (PFS) rates. In addition, more recently studies testing higher dosages of imatinib (800
mg per day) compared to standard dose imatinib or dose-adapted imatinib or imatinib plus
interferon have been reported to be able to induce better cytogenetic and molecular
responses, including the achievement of the deep molecular responses like MR4 and MR4,5
that are needed to attempt treatment free remission (TFR). The imatinib has become a generic
drug and that this has considerably lowered its cost allowing the use in patients all over the
world. Therefore, the choice of the front line CML therapy should be carefully calibrated and
tailored according to the patients’ profile and also taken in agreement with them after an
exhaustive information.
SCIENTIFIC PROGRAMME
SESSION I
OPTIMIZING
CYTOREDUCTION
SESSION II
MANAGEMENT OF CML
WITH TKI
SESSION III
MPN RISK
STRATIFICATION
INCLUDING VASCULAR
EVENTS
DEBATE 1
INTERFERON ALPHA
SHOULD BE FRONT LINE
THERAPY IN ALL ET/PV
PATIENTS
ROUNDTABLE 1
INFECTIONS IN
MYELOPROLIFERATIVE
DISORDERS, INCLUDING
CML
ROUNDTABLE 2
PREGNANCY AND
PARENTING
DEBATE 2
ALLOGENEIC STEM CELL
TRANSPLANTATION
SHOULD BE CONSIDERED
THIRD LINE OPTION IN
CHRONIC PHASE CML
SESSION IV
EVOLVING THERAPIES
IN MYELOFIBROSIS
SESSION V
MANAGEMENT OF
ADVANCED AND UNUSUAL
DISEASE (MPN AND CML)
SESSION VI
TREATMENT FREE
REMISSION IN CML
KEYNOTE LECTURE
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FO R A POSTER
PRESENTATION
DISCLOSURES