Prior Treatment Did Not Achieve Goals

The preceding step was a switch to a second-generation TKI — dasatinib, bosutinib, or nilotinib — taken after imatinib failure.

That regimen did not reach the required endpoints: complete cytogenetic response (CCyR) and major molecular response (MMR). This unmet response is what triggers escalation to this line.

Approach at This Line

After failure of a second-generation TKI, escalation to a third-generation TKI is the recommended direction. Full agent selection, sequencing, and transplant considerations are detailed in the complete structured protocol.

References

DOI: 10.1002/ajh.27443

In such patients, changing to a third-generation TKI is better.
We recommend using ponatinib 45 mg daily in T315I-mutated CML and 30 mg in non-T315I-mutated CML, with dose reductions to 15 mg daily once the BCR:ABL1 transcripts (IS) are ≤1%.
Based on these results, the FDA approved asciminib 40 mg BID for the treatment of CML-CP post-failure of 2+ TKIs without T315I or V299L mutations.
The recommended phase III dose of olverembatinib was 30 or 40 mg every other day in patients with CML-CP without or with the T315I mutation, respectively.
In patients with resistance to a second-generation TKI without guiding mutations or with T315I mutation, a third generation TKI and consideration of allo-HSCT are indicated.
After a median follow-up of 5 years, 60% of patients achieved MCyR (primary endpoint) at any time; 82% of those remained in MCyR at 5 years.

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Chronic Myeloid Leukemia After Second-Generation TKI Failure: What Is the Next Step?

References