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

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Achievement of an MMR seems to be significantly prognostic for RFS⁷
Achievement of CMR at 3 months has been demonstrated to be predictive of higher long-term survival⁶
Measuring MRD early, at the end of induction therapy, can identify patients at low risk of relapse, while measuring MRD at the end of consolidation therapy identifies patients at high risk of relapse¹
The ability to assess the potential risk of relapse using MRD helps to inform subsequent clinical decisions¹

Approximately 70–80% of patients with Ph+ ALL treated with 1G or 2G TKI revealed BCR-ABL1 mutations⁸
Point mutations can accumulate early in the disease course, even before treatment. While some mutant subclones persist at a low level, others expand rapidly, including mutations conferring TKI resistance^9–11
Patients with existing mutations have a higher likelihood of developing further mutations, including compound mutations^10–12

Sensitive methods of mutation detection can permit earlier identification of clinically relevant mutations that can expand and lead to TKI resistance^13–15
There are several methods with varying sensitivities that are able to detect low-level and compound mutations, although not all are used in routine clinical practice^16–19

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 mutations⁴
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^20,21
Together with T315I, compound mutations represent one of the biggest challenges in managing patients with Ph+ ALL²