What is the therapy for chronic myeloid leukemia (CML) that is resistant to Nilotinib (nilotinib)?

From the Guidelines

For chronic myeloid leukemia (CML) resistant to nilotinib, the recommended therapy is typically ponatinib, a third-generation tyrosine kinase inhibitor (TKI). According to the NCCN clinical practice guidelines in oncology 1, ponatinib is an option for patients with a T315I mutation and for those with disease that has not responded to several TKIs. The standard starting dose is 45 mg once daily, though dose reductions to 30 mg or 15 mg daily may be necessary based on toxicity 1.

Key Considerations

• Alternative options include bosutinib (500 mg once daily) 1, which has demonstrated activity in patients with CP-CML resistant/intolerant to multiple TKIs (imatinib, dasatinib, and nilotinib).
• For patients who fail multiple TKIs, allogeneic stem cell transplantation should be considered, particularly for younger patients in good health.
• Regular monitoring with BCR-ABL PCR testing every 3 months is essential to assess response 1.
• Treatment selection should be guided by mutation analysis to identify specific resistance mechanisms, particularly the T315I mutation which is resistant to most TKIs except ponatinib 1.

Adverse Events

• Serious arterial occlusive events (cardiovascular, cerebrovascular, and peripheral vascular) and venous thromboembolic events occurred in 31% and 6% of patients, respectively, in the PACE trial 1.
• Cardiovascular, cerebrovascular, and peripheral arterial occlusive events were reported in 16%, 13%, and 14% of patients, respectively 1.

From the FDA Drug Label

The definitions of resistance and intolerance to both dasatinib and nilotinib were similar to those for imatinib The efficacy endpoints for patients with CP CML previously treated with both imatinib and at least 1 additional TKI were the cumulative rate of attaining MCyR by Week 24 and the duration of MCyR. By Week 24 MCyR105 (40.1)29 (25.9) MCyR any time156 (59.5)45 (40.2)

Therapy for chronic myeloid leukemia that is resistant to nilotinib is bosutinib.

• The major cytogenetic response (MCyR) rate at any time for patients with CP CML previously treated with imatinib and at least 1 additional TKI (including nilotinib) was 40.2%.
• The median duration of bosutinib treatment was 9 months in patients with CP CML previously treated with imatinib and at least 1 additional TKI. 2

From the Research

Therapy for Chronic Myeloid Leukemia Resistant to Nilotinib

• For patients with chronic myeloid leukemia (CML) who are resistant to nilotinib, several treatment options are available, including other tyrosine kinase inhibitors (TKIs) such as bosutinib, dasatinib, and ponatinib 3, 4, 5.
• Dasatinib and ponatinib have been shown to be effective in patients with CML who are resistant to or intolerant of nilotinib, with response rates ranging from 40% to 60% 4, 5.
• Bosutinib is also an option for patients with CML who are resistant to or intolerant of nilotinib, although its efficacy in this setting is less well established 3, 4.
• Allogeneic hematopoietic stem cell transplant is a potentially curative option for patients with CML who are resistant to multiple TKIs, including nilotinib, although it is associated with significant risks and is typically reserved for patients with advanced disease or those who have failed multiple lines of therapy 3, 5.
• The choice of therapy for patients with CML who are resistant to nilotinib will depend on a variety of factors, including the patient's overall health, the presence of any comorbidities, and the specific characteristics of their disease 4, 5, 6.

Considerations for Treatment Selection

• When selecting a treatment for patients with CML who are resistant to nilotinib, it is essential to consider the potential benefits and risks of each option, including the likelihood of response, the potential for adverse effects, and the impact on quality of life 3, 4, 5.
• The presence of specific mutations, such as the T315I mutation, may also influence the choice of therapy, as some TKIs are more effective than others against certain mutations 5, 6.
• Close monitoring and follow-up are crucial to ensure that patients receive the most effective treatment possible and to minimize the risk of adverse effects 3, 7.