Successful management of pregnancy and hepatic toxicity in a CML female patient treated with nilotinib : a case report and a review
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nilotinib, discontinuation, chronic myeloid leukemia, imatinib, pregnancy, hepatopathy.
We report a case of a young patient with HBV hepatopathy, diagnosed with CML in March 2006 and treated with imatinib 400mg/die as first line therapy with concomitant Lamivudine. Patient obtained a complete hematologic response (CHR) in 2 months, complete cytogenetic response (CCyR) in six months and major molecular response (MMR) at 24 months. After three years of treatment she became imatinib intolerant and resistant. In November 2009 patient started nilotinib 400mg/BID. Patient tolerated well the new molecule never experiencing hepatic impairment. After switching to nilotinib she reached in 12 months transcript reduction more than 3 log (MMR). Even if patient had been informed of the need of continuous therapy and to use effective methods of contraception during TKI treatment, in 2012 she decided to plan a pregnancy. In August 2012 a MR4 was documented and treatment discontinued before starting pregnancy. She was observed throughout her pregnancy. The disease remained stable achieving an undetectable transcript level; she delivered a healthy boy in September 2013. Treatment with nilotinib was re-started three months after delivery and she is still in molecular remission (MR5). A complete discussion of the case and the available literature will be presented.
2 Hochhaus A, O’Brien SG, Guilhot F, Druker BJ, Branford S, Foroni L et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia 2009; 23: 1054–1061.
3. Deininger M, O'Brien SG, Guilhot F, Goldman JM, Hochhaus A, Hughes TP, Radich JP, Hatfield AH, Mone M, Filian J, Reynolds J, Gathmann I, Larson RA, Druker BJ, Blood. 2009;114(22):462 [abstract 1126].
4. Baccarani M, Cortes J, Pane F, Niederwieser F, Saglio G, Apperley J, Cervantes F, Deininger M, Gratwohl A, Guilhot F, Hochhaus A, Horowitz M, Hughes T, Kantarjian H, Larson R, Radich J, Simonsson B, Silver RT, Goldman J, Hehlmann R Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet. 2009 J Clin Oncol 27:6041-6051
5. Giles FJ, le Coutre PD, Pinilla-Ibarz J nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study Leukemia (2012) 1 – 6
6. Deininger M, O’Brien SG, Guilhot F, et al: International Randomized Study of interferon Vs STI571 (IRIS) 8-Year Follow up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. 51st ASH Annual Meeting and Exposition, New Orleans, LA, December 5-8, 2009 (abstr 1126).
7. Hahn EA, Glendenning GA, Sorensen MV et al. Quality of life in patients with newly diagnosed chronic phase chronic myeloid leukemia on imatinib versus interferon alfa plus low-dose cytarabine: results from the IRIS Study. J Clin Oncol. 2003 Jun 1;21(11):2138-46.
8. Pinilla-Ibarz J, Cortes J, Mauro MJ. Intolerance to tyrosine kinase inhibitors in chronic myeloid leukemia: definitions and clinical implications. Cancer. 2011;117(4):688-697.
9. Efficace F, Baccarani M, Breccia M et al. Health-related quality of life in chronic myeloid leukemia patients receiving long-term therapy with imatinib compared with the general population. Blood 2011 118: 4554-4560.
10. Hagop M. Kantarjian, Francis J. Giles, Kapil N. Bhalla nilotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results Blood 2011 117: 1141-1145
11. Kantarjian H, O'Brien S, Shan J, Huang X, Garcia-Manero G, Faderl S, et al. Cytogenetic and molecular responses and outcome in chronic myelogenous leukemia: Need for new response definitions? Cancer 2008;112:837–45.
12. Verma D, Kantarjian HM, Shan J, O'Brien S, Verma A, Jabbour E, et al. Sustained complete molecular response to imatinib in chronic myeloid leukemia (CML): A target worth aiming and achieving? Blood 2009;114 (abstr 505).
13. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 2013;122:872–84.
14. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Chronic Myelogenous Leukemia. Version 4.2013.
15. Mahon FX, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, Etienne G, Reiff J, Rousselot P Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete
molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial Lancet Oncol 2010; 11: 1029–35
16. Pye SM, Cortes J, Ault P, Hatfied A, Kantarjian H, Pilot R, Rosti G, Apperly J. The effects of imatinib on pregnancy outcome. Blood 2008;111:5505-5508
17. Abruzzese E, Trawinska MM, Perrotti AP, De Fabritiis P. Tyrosine kinase inhibitors and pregnancy. 2014 Apr 7;6(1): e2014028. doi: 10.4084/MJHID.2014.028. Mediterr J Hematol Infect Dis.. eCollection 2014. Review
18. Shah NP, Tran C, Lee FY, et al. Science. 2004;305:399-401
19. Pons JC, Lebon P, Frydman R, Delfraissy JF. Pharmacokinetics of interferon-alpha in pregnant women and fetoplacental passage. Fetal Diagn Ther 1995; 10: 7–10.
20. Patel M, Dukes IA, Hull JC. Use of hydroxyurea in chronic myeloid leukemia during pregnancy: A case report. Am J Obstet Gynecol 1991;165: 565–566.
21. Webb MJ, Jafta D. Imatinib use in pregnancy. Turk J Haematol. 2012, Dec;29(4):405-8.
22. Berveiller P, Andreoli A, Mir O, Anselem O, Delezoide AL, Sauvageon H, Chapuis N, Tsatsaris V. A dramatic fetal outcome following transplacental transfer of dasatinib. Anticancer Drugs. 2012; Aug;23(7):754-7