Chronic Myeloid Leukemia When Third- and Fourth-Line TKI Therapy Has Failed

This protocol applies to patients with chronic myeloid leukemia whose disease has not been adequately controlled despite treatment with third- or fourth-line tyrosine kinase inhibitor therapy, including agents used in later lines of treatment.

Prior Treatment Failure — Escalation Trigger

The previous treatment line included agents such as asciminib, ponatinib, or olverembatinib (where approved). Escalation to this protocol is indicated when that line failed to achieve the key molecular response milestone of a BCR::ABL1^IS of 1% or lower — the threshold associated with optimised long-term outcomes — at the expected timepoints.

Next Treatment Approach (partial — full protocol below)

For patients who have not responded to or cannot tolerate the available TKI options, allogeneic stem cell transplantation is considered the next treatment step. The specific eligibility criteria, timing, and conditioning approach are defined in the full structured protocol.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1038/s41375-025-02664-w

The use of alloSCT in CML decreased dramatically following the introduction of TKI, but it remains an important therapeutic modality for patients in CP resistant to third and/or fourth generation TKI, or intolerant to all available TKI and for those who present in or progress to, BP.
Where possible we recommend myeloablative conditioning.

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