Chronic myeloid leukemia
ICD-10 C92.1 · ICD-11 2B33.2

Chronic Myeloid Leukemia: Treatment When First-Line TKI Therapy Did Not Achieve the Required Molecular Response

Patients with chronic myeloid leukemia who received a first-line tyrosine kinase inhibitor (TKI) but did not reach the defined BCR::ABL1 molecular response milestones require escalation to a structured second-line protocol. This page outlines that scenario and the framework that applies.

When First-Line TKI Is Considered to Have Failed

First-line therapy — which may include imatinib, dasatinib, nilotinib, bosutinib, asciminib, or radotinib — is considered insufficient when the following BCR::ABL1IS milestones are not met:

  • BCR::ABL1IS fails to reach 10% or lower at 3 months
  • BCR::ABL1IS fails to reach 1% or lower at 6 months
  • BCR::ABL1IS fails to reach 0.1% or lower (major molecular response) at 12 months
Second-Line Approach — Partial Overview

The next step involves a second-line tyrosine kinase inhibitor, with selection informed by which agent was used in the first line and by BCR::ABL1 mutation testing. The complete decision framework — including which agents apply after which prior therapies, the role of specific mutations, and the full selection algorithm — is contained in the structured protocol.

Response Goals for This Line

The BCR::ABL1IS milestones for second-line therapy are the same as for first-line treatment:

Instant Access to Structured Evidence-Based Regimens
References

After first-line imatinib and in the absence of specific BCR::ABL1 mutations any suitable 2GTKI can be used as they appear equally effective in second-line, although no studies have directly compared the 2GTKI with each other.

After resistance to a first-line 2GTKI and in the absence of specific BCR::ABL1 mutations, the use of an alternative 2GTKI is rarely successful in achieving molecular responses and consideration should be given to early use of ponatinib or asciminib.

Responses (milestones) to second-line treatment are the same as to first-line treatment.

DOI: 10.1038/s41375-025-02664-w
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