Risk of developing resistance to BCR-ABL
TKI treatment

The risk of developing resistance to TKI treatment varies by disease stage and prior treatment. Resistance is rarely seen in patients in early chronic-phase CML who are on initial treatment, but it occurs more often in patients in blast-phase CML. ¹

In de novo patients with chronic-phase CML, the risk of developing resistance to treatment with a BCR-ABL TKI is low, and the annual rate of disease progression decreases over time as long as continuous treatment is maintained¹
In a long-term study of BCR-ABL TKI treatment, most patients maintained their response to treatment, and only a small minority had disease progression associated with mutations in BCR-ABL²

How frequent are resistance-conferring mutations in CML?

In studies of CML patients treated with a TKI

Durable responses can be expected in 8 out of 10 patients.^2,3

CML Therapy - Developing Resistance

Among the minority of patients who develop treatment resistance.

Fewer than half will have detectable mutations in BCR-ABL.^3,4

Among the dozens of BCR-ABL mutations that have been
identified...

Only one mutation, T315I, present in approximately 2% of
treatment-resistant patients, is associated with resistance to all of the currently available TKIs.^3,5 CML Therapy - Developing Resistance2

Patients who have an increased risk of developing treatment resistance include:

Patients with chronic-phase CML who previously failed treatment with interferon-a (estimated 2-year incidence of treatment resistance: 10% to 20%)¹
Patients with accelerated-phase CML (estimated 2-year incidence of treatment resistance: 40% to 50%)¹
Patients with blast-phase CML or acute lymphoblastic leukemia (estimated 2-year incidence of treatment resistance: 70% to 80%)¹

Padmanabhan S, Ravella S, Curiel T, Giles F. Current status of therapy for chronic myeloid leukemia: a review of drug development. Future Oncol. 2008;4(3):359-377.
Druker BJ, Guilhot F, O'Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355(23):2408-2417.
Hochhaus A, Baccarani M, Deininger M, et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008;22(6):1200-1206
Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542-51.
Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. Supplementary appendix. www.http://content.nejm.org/cgi/content/full/354/24/ 2542/DC1.

Risk of developing resistance to BCR-ABL TKI treatment

Risk of developing resistance to BCR-ABL
TKI treatment