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Why is it important to think about monitoring and mutation testing when treating patients with cml and what is important to consider?

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Identifying patients at risk of failing, or who have failed, TKI treatment allows physicians to change therapy earlier in the treatment course to improve long-term outcomes^1,2

Molecular monitoring by RQ-PCR is recommended at baseline and at least every 3 months throughout treatment¹
Monitoring schedule has to be adapted for patients who cease therapy (TFR patients)¹

BCR-ABL1 kinase domain mutations are found in:
- Up to 63% of patients with imatinib resistance⁷
- 14–33% of patients with resistance to second-line 2G TKI⁵
Timely detection of mutations known to confer TKI resistance can facilitate appropriate clinical decisions^1,3,4

Mutation testing should be performed:¹
- At diagnosis: only in CML patients who present in de-novo accelerated- or blast phase
- During therapy: in all CML patients with failure/resistance and always when switching TKI
Conventional Sanger (direct) sequencing is the currently recommended method for mutation testing, but cannot detect mutations present in less than 20% of BCR-ABL1 transcripts (low-level mutations)⁸
There are several methods with varying sensitivities that are able to detect low-level mutations^8-11
Sensitive methods of mutation detection, such as NGS, provide a more accurate picture of BCR-ABL1 mutation status in CML patients with failure or warning¹²

Conventional Sanger sequencing

15–25%

Denaturing HPLC

0.1–10%

NGS

0.5–1%

Mass spectrometry

0.05–0.5%

ASO-PCR

0.001–0.01%

Based on mutation testing results, the most appropriate TKI should be selected – different TKls are effective against different mutations^1,3-5
Choosing an inappropriate TKI leads to a high risk of subsequent treatment failure with clonal expansion of the resistant mutant and a greater likelihood of developing additional mutations, including compound mutations^8,12,13