Chronic Myeloid Leukemia: Treatment

Chronic Myeloid Leukemia: overview

This algorithm sequences tyrosine kinase inhibitor therapy for chronic myeloid leukemia by disease phase and response. In chronic phase, frontline therapy is selected by risk: imatinib for low-risk disease (IRIS), and a second-generation TKI such as dasatinib or nilotinib for intermediate or high-risk disease (DASISION and ENESTnd).

For resistance or intolerance, the chart offers a switch to an alternate second-generation TKI chosen according to mutation testing, ponatinib for the T315I mutation (PACE), or asciminib, a STAMP inhibitor (ASCEMBL). The site's ASCEMBL summary reports a higher major molecular response rate at 24 weeks with asciminib than with bosutinib in third-line or later chronic phase CML (25.5% vs 13.2%), with the advantage sustained on longer follow-up and fewer discontinuations for intolerance, so that asciminib has effectively replaced bosutinib in that setting. Accelerated or blast phase disease is managed with curative intent: a TKI with or without chemotherapy, followed by allogeneic transplant.

Trials behind this algorithm

• IRIS trial Stephen G O'Brien et al, NEJM, 2003; PMID:12637609
• DASISION trial Hagop Kantarjian et al, NEJM, 2010; PMID:20525995
• ASCEMBL Rea D et al, Blood, 2021; PMID: 34407542

Background reading: Chronic myeloid leukemia (CML) board review notes.