Revisión del tratamiento de LMC, asi como estudios que lo apoyan

1. Fabio Enrique Parada Cabrera
Tratamiento de la
Leucemia mieloide crónica

2. National Center for Biotechnology Information. PubChem Compound Database; CID=24826799,
https://pubchem.ncbi.nlm.nih.gov/compound/24826799 (accessed Mar. 20, 2018).
Inhibidores de la Tirosin Kinasa
Fármacos de primera generación - Imatinib
Fármacos de segunda generación – Bosutinib y Dasatinib:
diseñados para superar la resistencia al imatinib, y por eso
fue llamado de segunda generación.
Tercera Generación – Ponatinib: Fue diseñado
específicamente para tratar la mutación T315I y otras
resistencias de la tirosina cinasa BCR-ABL.

3. National Center for Biotechnology Information. PubChem Compound Database; CID=24826799,
https://pubchem.ncbi.nlm.nih.gov/compound/24826799 (accessed Mar. 20, 2018).
Evaluación inicial y elección de
tratamiento
The treatment of chronic
myeloid leukemia (CML) is
based upon the specific
disease phase. There are
three general disease phases:
●Chronic stable phase
●Accelerated phase
●Blast crisis
Selection of a TKI
for initial treatment
of CML in CP is
informed by CML
prognostic score,
side effect profiles ,
comorbid illnesses,
and cost.

4. National Center for Biotechnology Information. PubChem Compound Database; CID=24826799,
https://pubchem.ncbi.nlm.nih.gov/compound/24826799 (accessed Mar. 20, 2018).

5. Mauro MJ, Druker BJ. STI571: targeting BCR-ABL as therapy for CML. Oncologist 2001; 6:233.
Imatinib inhibits
several tyrosine
kinases, including
p210BCR-ABL,
p190BCR-ABL, v-
ABL, c-ABL, C-kit,
and PDGF
receptor.
Imatinib

6. M. D. Anderson data; 1884 patients from 1965 to 2008.)
Imatinib una revolución en tratamiento
de LMC

7. N Engl J Med 2017;376:917-27. DOI: 10.1056/NEJMoa1609324
Study of Interferon and STI571 (IRIS)

8. N Engl J Med 2017;376:917-27. DOI: 10.1056/NEJMoa1609324
Study of Interferon and STI571 (IRIS)

9. N Engl J Med 2017;376:917-27. DOI: 10.1056/NEJMoa1609324
Study of Interferon and STI571 (IRIS)

10. N Engl J Med 2017;376:917-27. DOI: 10.1056/NEJMoa1609324
Study of Interferon and STI571 (IRIS)

11. Chouchani,A. et al. Unifying Mechanism for Mitochondrial Superoxide Production during
Ischemia-Reperfusion Injury.Cell Metabolism 23, February 9, 2016
Chronic myeloid leukemia (CML)-study
IV

12. Leukemia (2017) 31, 2398–2406
CML-study IV

13. Leukemia (2017) 31, 2398–2406
CML-study IV

14. Leukemia (2017) 31, 2398–2406
CML-study IV

15. Leukemia (2017) 31, 2398–2406
CML-study IV

16. Leukemia (2017) 31, 2398–2406
CML-study IV

17. Milojkovic D, Apperley J. Mechanisms of Resistance to Imatinib and Second-Generation Tyrosine
Inhibitors in Chronic Myeloid Leukemia. Clin Cancer Res 2009; 15:7519.
Resistencia
Primary resistance — There is limited information about mechanisms
of primary resistance. There are two main mechanisms that are
theoretically possible:
●Insufficient inhibition of the BCR-ABL1 tyrosine kinase
●Decreased numbers of normal hematopoietic cells resulting in
failure to recover normal blood counts
Secondary resistance — The mechanisms of secondary resistance are
varied but most commonly involve reactivation of BCR-ABL1 signaling
and/or the activation of other signaling pathways, such as SRC kinase

18. Blood First Edition Paper, December 23, 2004; DOI 10.1182/blood-2004-08- 3097.
Resistencia

19. Blood. 2012;120(19):3898. Epub 2012 Aug 22.
Dasatinib

20. Blood. 2012;120(19):3898. Epub 2012 Aug 22.
Dasatinib
•The proportion of patients achieving a complete
cytogenetic remission rate was superior with DAS
(84% vs 69%)
•Overall and progression-free survival was similar in
the 2 arms.
•Among patients who achieved hematologic CR, 3-
year relapse-free survival was 91% with DAS and 88%
with IM 400 mg

21. Leukemia (2016) 30, 1044–1054
Nilotinib

22. Leukemia. 2016 May;30(5):1044-54. doi: 10.1038/leu.2016.5. Epub 2016 Feb 3
Nilotinib
•Higher rates of major molecular response (MMR) at
12 months (44 and 43 versus 22 percent,
respectively).
•Higher cumulative rates of complete cytogenetic
response (CCyR) at 24 months (87 and 85 versus 77
percent, respectively).
•Estimated overall survival (OS) rates were similar
between nilotinib 300 mg twice daily and imatinib (94
versus 92 percent at five years; hazard ratio 0.80; 95%
CI 0.43-1.49).

23. Leukemia (2016) 30, 1638–1647
¿Cuándo podemos detener el
tratamiento?

24. Chouchani,A. et al. Unifying Mechanism for Mitochondrial Superoxide Production during
Ischemia-Reperfusion Injury.Cell Metabolism 23, February 9, 2016

25. Leukemia. 2016 May;30(5):1044-54. doi: 10.1038/leu.2016.5. Epub 2016 Feb 3
Gracias