CML & PH+ All: There is so much more to know CML & PH+ All: There is so much more to know Explore

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

Think Test Treat

WHY?

  • MRD is an important prognostic factor for outcomes in Ph+ ALL1,2,5

WHAT?

  • 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

Think Test Treat

WHY?

  • Approximately 80-90% of patients with Ph+ ALL who relapse on imatinib have BCR-ABL1 mutations (most commonly P-loop or T315I)2

  • 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 resistance6,7

  • Patients with existing mutations have a higher likelihood of developing further mutations, including compound mutations6-8

WHAT?

  • Sensitive methods of mutation detection permit earlier identification of clinically relevant mutations that can expand and lead to TKI resistance9-11

  • 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 practice12-15

Mutation testing methods and associated sensitivities

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%

Think Test Treat

WHY?

  • Based on mutation testing results, the most appropriate TKI can 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 mutations16,17

  • Together with T315I, compound mutations represent one of the biggest challenges in managing patients with Ph+ ALL2

WHAT?

  • Mutation testing results should inform clinical decisions4

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For further information, please contact Incyte Medical Information: eumedinfo@incyte.com