Canterbury DHB

Management of Suboptimal Response, Treatment Failure, and Loss of Response

Review compliance, drug-drug interactions and tolerance of TKI. If on imatinib, consider checking an imatinib level.

If response is suboptimal, review the patient at least 3 monthly.

Patients with persisting suboptimal response, treatment failure, or loss of response

These patients should undergo bone marrow biopsy, cytogenetics with G-banding, and TKI mutational analysis. The latter may give an indication of which second-line TKI may be most appropriate for patients who need to switch from imatinib (see European LeukemiaNet guidelines,⁷ table 2, page 4).

Otherwise, determine second-line therapy by the patient's co-morbidity and side-effect profile.

Another option for patients who have suboptimal response, but are tolerating imatinib well, is to increase the imatinib dose (up to max 800mg/day) and reassess at 3 months.

Data from Tim Hughes in Adelaide indicates:

• Early molecular response at 3 months predicts for subsequent molecular response.
• Patients who:
  • have a greater than 2-log reduction by 3 months are likely to achieve an MMR (3-log reduction) after 24 months of imatinib.
  • have a 1 to 2-log reduction (51%) may still achieve an MMR.
  • fail to have a 1-log reduction have a very low probability of achieving an MMR and do not do so well on imatinib.

Patients with suboptimal response, treatment failure, or loss of response following use of dasatinib or nilotinib

As of July 2018, there are limited options for these patients.

Bosutinib or ponatinib are recommended in the ESMO and NCCN guidelines, but are not funded in New Zealand. Access via Named Patient Pharmaceutical Assessment (NPPA), compassionate programmes, or other access schemes which may require partial patient payment may be an option. Ponatinib is considered the drug choice in patients with T315 mutation.

Allogeneic SCT remains a therapeutic option for patients in CML CP who fail at least two TKIs, or are harbouring the T315I mutation (especially if ponatinib failed or is unavailable). Consider patients with a high risk for transformation for alloSCT, since the outcome of alloSCT after transformation is unfavourable. The only curative option for patients in BP disease is alloSCT. AlloSCT should also be considered early in patients developing AP on a TKI, or high-risk patients with insufficient treatment response. However, alloSCT is not usually advocated for advanced disease with a high transplant risk. Ongoing drug treatment or best supportive care might be the better option in this setting.

Topic Code: 533093