Ph+ CML Disease Overview
Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) is a disease caused by an abnormal fusion protein, BCR-ABL
Chronic myeloid leukemia (CML) is characterized by the presence of a Philadelphia (Ph) chromosome, which is a translocation of chromosomes 9 and 22.1,2 This translocation causes BCR and ABL genes to fuse. The BCR-ABL gene creates a fusion protein—the BCR-ABL protein—the molecular marker of CML, which continuously stimulates the cells to grow giving rise to the leukemic clone.2 This BCR-ABL protein is a constitutively active tyrosine kinase domain, which promotes cell proliferation.3 Evidence confirms that the unregulated activity of the ABL tyrosine kinase in BCR-ABL is the cause of Ph+ CML.4 For this reason, the BCR-ABL tyrosine kinase domain remains ideal for a targeted therapeutic approach.
Translocation of Chromosomes 9 and 221
Keeping Ph+ CML patients in the chronic phase is vital5
In ENESTnd, the median survival of patients who progressed to AP/BC was only 10.5 months, illustrating the importance of maintaining patients with Ph+ CML in the chronic phase.5,6
Survival after progression to AP/BC in ENESTnd
(n/N = 34/846)5*
*ENESTnd patients (N=846) were followed for survival and progression every 3 months; planned duration of follow-up is 10 years.5,6
AP/BC, accelerated phase/blast crisis; MMR, major molecular response.
ENESTnd is a Phase III, randomized, open-label, multicenter study of 846 patients with newly diagnosed Ph+ CML in chronic phase who received TASIGNA 300 mg BID, TASIGNA 400 mg BID, or imatinib 400 mg QD. The primary endpoint was MMR at 12 months.
- Faderl S, et al. N Engl J Med. 1999;341(3):164-172;
- Sawyers CL. N Engl J Med. 1999;340(17):1330-1340;
- Ren R. Nat Rev Cancer. 2005;5(3):172-183;
- Hochhaus A, et al. Leukemia. 2002;16(11):2190-2196;
- Larson RA, et al. Leukemia. 2012;26(10):2197-2203;
- TASIGNA® (nilotinib) Summary of Product Characteristics. Basel, Switzerland: Novartis Pharma AG; May 2017.