1. La tossicità degli
altri TKI
Dott. Michele Cedrone

3. Proposed definition of intolerance
A patient has TKI intolerance if one or more of the following
criteria have been met:
 any life-threatening grade 4 nonhematological toxicity;
 any grade 3/4 nonhematological toxicity that has recurred
despite dose reduction;
 any grade 2 nonhematological toxicity that persists for more
than a month despite optimal supportive measures;
 grade 3-4 hematological toxicity that is unresponsive to
supportive measures and would require dose reductions
below the accepted minimal effective dose.
Educational Session ASH 2012
Managing Chronic Myeloid Leukemia as a Chronic Disease
Andreas Hochhaus

5. Le Coutre P, Rea D, Abruzzese E, Dombret H, Trawinska MM,
Herndlhofer S, et al. Severe peripheral arterial disease during nilotinib therapy.
J Natl Cancer Inst. 2011;103(17):1347-8.

7. Durata mediana
Del trattamento 5,8 anni
832 paz
età mediana 51 anni (18-94)

10. Long-term toxic effects associated with imatinib appeared
to be modest because only 2.3% of patients stopped
imatinib because of side effects
NSAEs related to treatment were frequent events, with
more than 50% of patients having at least one NSAE
after 8 years of treatment, suggesting that patients
treated with imatinib, although not experiencing severe
toxic effects, frequently suffer from side effects that,
although not serious, can reduce quality of life.

11. ENESTnd – DASISION
studi diversi

12. MMR: confronto a 5 anni
DASISION
ENEST nd

13. Pazienti ancora in trattamento

14. DASISION follow-up a 4 anni

15. DASISION evaluating long-term efficacy and
safety outcomes
Minimum of 5 years of follow-up since randomization

16. Characteristics and Management
of Pleural Effusion

18. On the whole, data on 172 unselected consecutive elderly patients with CML in
CP resistant/intolerant to imatinib and treated with dasatinib were collected by 27
centres in Italy
During treatment, 52 patients (30.2%) developed a pleural effusion, after a
median time from dasatinib initiation of 11.0months (IR 3.6–18.6);

19. As expected in a real-life cohort of
elderly patients treated with dasatinib,
pleural effusions were more common than
in previous reports
• There was a wide range in the time
interval from dasatinib start to pleural
effusion occurrence;
• However, pleural effusions were
clinically manageable in the majority of
patients;
• Permanent discontinuations
of dasatinib treatment due to this adverse
event were quite rare (6.4% of all elderly
patients treated with dasatinib);
• pleural effusions did not seem to
affect treatment efficacy, with
comparable rates of cytogenetic
response and overall survival

27. Grey shading indicates P value <005 for incidence (all
grades) with bosutinib versus imatinib:
Lighter grey shading indicates AEs more common with
bosutinib;
Darker grey shading indicates AEs more common with
imatinib.

28. Bosutinib Imatinib
Pazienti che hanno interrotto il trattmento 37% 29%
Interruzione per SAE 25% 9%
Interruzione nei primi 12 mesi 19% 6%

30. Unique profiles of clinically overt recurrent non-hematologic adverse
events in patients with CML treated with BCR/ABL1-targeting TKIs

31. Variables and comorbidities that increase the risk of occurrence of clinically
severe adverse events in CML patients treated with second-generation TKIs

32. Strategies aimed at reducing the risk of VAE development in patients with CML

34. 15/05/2015