Nilotinib efficacy in a patient resistant to imatinib

Abstract

Imatinib, a BCR-ABL inhibitor, is the standard of care for the first-line treatment of patients with chronic-phase CML. Despite the optimal results, some patients develop resistance to imatinib. For these patients, the second-generation tyrosine kinase inhibitors represent effective therapeutic options. Here, we describe a report about a young patient with CML developing resistance to imatinib due to BCR-ABL kinase domain mutations. After six months of treatment with imatinib 400 mg daily, the patient had complete cytogenic response, while at 12 months he had a sub-optimal molecular response, that is a “warning” according to the European LeukemiaNet guidelines (both 2006 and 2009). At 29 months, persisting the sub-optimal molecular response, we decided to increase the imatinib dose up to 800 mg daily. Even after the dose escalation, the patient couldn’t achieve a major molecular response. Therefore we subjected him to a mutation screening, that highlighted L248V mutation. After switching to nilotinib the patient has resulted in complete cytogenic response and major molecular response.

Keywords

• Chronic myeloid leukemia
• Imatinib resistance
• BCR-ABL mutations
• Nilotinib