Nilotinib as First-line Treatment of Ph+ CML in Early Chronic Phase

Summary

Treating Ph pos CML with Imatinib is very effective since the majority of the patients achieve a complete cytogenetic response and a major molecular response and are alive and progression-free after 5 years. However, the great majority of responding patients are not leukemia-free and may be at risk of progression, molecular, cytogenetic and clinical, at any time. In case of disease progression due to Imatinib failure, nilotinib has been found to be very effective, as expected from the preclinical profile of the drug, that is much more potent against BCR-ABL and inhibits nearly all the imatinib-resistant BCR-ABL mutants. For these reasons, nilotinib is going to be registered for the treatment of imatinib-resistant CMl patients. For the same reasons, nilotinib is expected to be more efficient than imatinib also front-line, based on the principle that we should aim at preventing the emergence of resistance better that at treating resistance once it has emerged. This expectation can be tested safely, because the "toxicity profile" of Nilotinib may be even more convenient than that of Imatinib, due to the lower frequency of edema and fluid retention.

Timeline

Start

2007-06-23

Primary completion

2018-04-30

Completion

2018-04-30

Publications

• Background Calabretta B, Perrotti D. The biology of CML blast crisis. Blood. 2004 Jun 1;103(11):4010-22. doi: 10.1182/blood-2003-12-4111. Epub 2004 Feb 24.
• Background Barnes DJ, Melo JV. Management of chronic myeloid leukemia: targets for molecular therapy. Semin Hematol. 2003 Jan;40(1):34-49. doi: 10.1053/shem.2003.50002.
• Background Goldman JM, Melo JV. Chronic myeloid leukemia--advances in biology and new approaches to treatment. N Engl J Med. 2003 Oct 9;349(15):1451-64. doi: 10.1056/NEJMra020777. No abstract available.
• Background Goldman JM, Marin D, Olavarria E, Apperley JF. Clinical decisions for chronic myeloid leukemia in the imatinib era. Semin Hematol. 2003 Apr;40(2 Suppl 2):98-103; discussion 104-13. doi: 10.1053/shem.2003.50049.
• Background Goldman JM, Marin D. Management decisions in chronic myeloid leukemia. Semin Hematol. 2003 Jan;40(1):97-103. doi: 10.1053/shem.2003.50009.
• Background Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options. Blood. 2001 Oct 1;98(7):2039-42. doi: 10.1182/blood.v98.7.2039.
• Background Baccarani M, Russo D, Rosti G, Martinelli G. Interferon-alfa for chronic myeloid leukemia. Semin Hematol. 2003 Jan;40(1):22-33. doi: 10.1053/shem.2003.50004.
• Background Martinelli G, Soverini S, Rosti G, Cilloni D, Baccarani M. New tyrosine kinase inhibitors in chronic myeloid leukemia. Haematologica. 2005 Apr;90(4):534-41.
• Background Rosti G, Martinelli G, Bassi S, Amabile M, Trabacchi E, Giannini B, Cilloni D, Izzo B, De Vivo A, Testoni N, Cambrin GR, Bonifazi F, Soverini S, Luatti S, Gottardi E, Alberti D, Pane F, Salvatore F, Saglio G, Baccarani M; Study Committee, Italian Cooperative Study Group for Chronic Myeloid Leukemia; Writing Committee, Italian Cooperative Study Group for Chronic Myeloid Leukemia. Molecular response to imatinib in late chronic-phase chronic myeloid leukemia. Blood. 2004 Mar 15;103(6):2284-90. doi: 10.1182/blood-2003-07-2575. Epub 2003 Nov 26.
• Gugliotta G, Castagnetti F, Breccia M, Levato L, D'Adda M, Stagno F, Tiribelli M, Salvucci M, Fava C, Martino B, Cedrone M, Bocchia M, Trabacchi E, Cavazzini F, Usala E, Russo Rossi A, Bochicchio MT, Soverini S, Alimena G, Cavo M, Pane F, Martinelli G, Saglio G, Baccarani M, Rosti G; GIMEMA CML Working Party. Long-term outcome of a phase 2 trial with nilotinib 400 mg twice daily in first-line treatment of chronic myeloid leukemia. Haematologica. 2015 Sep;100(9):1146-50. doi: 10.3324/haematol.2015.129221. Epub 2015 Jun 25.
• Castagnetti F, Gugliotta G, Baccarani M, Breccia M, Specchia G, Levato L, Abruzzese E, Rossi G, Iurlo A, Martino B, Pregno P, Stagno F, Cuneo A, Bonifacio M, Gobbi M, Russo D, Gozzini A, Tiribelli M, de Vivo A, Alimena G, Cavo M, Martinelli G, Pane F, Saglio G, Rosti G; GIMEMA CML Working Party. Differences among young adults, adults and elderly chronic myeloid leukemia patients. Ann Oncol. 2015 Jan;26(1):185-192. doi: 10.1093/annonc/mdu490. Epub 2014 Oct 30.
• Lenaerts T, Castagnetti F, Traulsen A, Pacheco JM, Rosti G, Dingli D. Explaining the in vitro and in vivo differences in leukemia therapy. Cell Cycle. 2011 May 15;10(10):1540-4. doi: 10.4161/cc.10.10.15518. Epub 2011 May 15.
• Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, Capucci A, Cedrone M, Fava C, Intermesoli T, Cambrin GR, Stagno F, Tiribelli M, Amabile M, Luatti S, Poerio A, Soverini S, Testoni N, Martinelli G, Alimena G, Pane F, Saglio G, Baccarani M; GIMEMA CML Working Party. Nilotinib for the frontline treatment of Ph(+) chronic myeloid leukemia. Blood. 2009 Dec 3;114(24):4933-8. doi: 10.1182/blood-2009-07-232595. Epub 2009 Oct 12.

Drugs

Indications