What changed: Chronic myeloid leukaemia (CML)

When this page itself was last checked or edited.

Newly diagnosed Ph+ CML in chronic phase (ASC4FIRST)

ASC4FIRST: higher MMR at 48 weeks than investigator-selected TKI; FDA accelerated approval October 2024.

CML after ≥2 prior TKIs; T315I CML

Chronic myeloid leukaemia (chronic or accelerated phase) with the T315I mutation after prior tyrosine kinase inhibitors

ASCEMBL vs bosutinib in third line.

Treatment-free remission attempt after ≥3-5 years of TKI and ≥2 years of MR4 or better, with monthly PCR for the first six months (EURO-SKI); restart on loss of MMR.

Switch TKI guided by mutation analysis; ponatinib or asciminib for T315I; allogeneic HSCT if two or more TKIs fail or in advanced phase.

Imatinib 400 mg, or a second-generation TKI (dasatinib, nilotinib, bosutinib), or asciminib (ASC4FIRST, approved 2024). Choice by comorbidity and treatment goal; monitor BCR-ABL1 IS at 3, 6, 12 months against ELN milestones. (NCCN Category 1 (imatinib, dasatinib, nilotinib, bosutinib, asciminib))

Newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia, chronic phase

EURO-SKI: about half of patients stopping TKI stay in remission.

Newly diagnosed Ph+ CML chronic phase

Confirmed: the accelerated approval of 2012 converted to traditional approval 1.3 years after it was granted.

Ph+ CML

Resistant CML/Ph+ ALL

Accelerated approval on a surrogate endpoint, with a confirmatory trial required.

Ph+ CML after prior TKI

Chronic or accelerated phase CML resistant or intolerant to two or more TKIs (accelerated; full approval 2014)

CML and Ph+ ALL resistant to prior TKIs or with T315I

A milestone in how this cancer is treated.

Newly diagnosed Ph+ CML chronic phase

Dasatinib produced higher confirmed complete cytogenetic and major molecular response rates at 12 months than imatinib, with no difference in five-year overall survival.

Ph+ CML

Ph+ CML, chronic or accelerated phase, resistant/intolerant to imatinib

CML and Ph+ ALL resistant or intolerant to imatinib

Dasatinib (2006) and nilotinib (2007) approved for resistance; later first line (DASISION, ENESTnd).

Conditioning before haematopoietic progenitor cell transplantation (Busilvex)

Chronic myeloid leukaemia: first targeted kinase inhibitor, approved in under 3 months

Chronic myeloid leukaemia

FDA approval in under three months; IRIS (2003) confirms superiority over interferon-cytarabine.

Conditioning with cyclophosphamide before allogeneic HPC transplantation for CML (Busulfex)

Druker's phase 1 trial of STI571: complete haematologic responses in nearly every chronic-phase patient.

Daley, Van Etten and Baltimore demonstrate the fusion kinase is sufficient to cause a CML-like disease.

Janet Rowley shows the Philadelphia chromosome is a reciprocal translocation.

Remission induction in acute non-lymphocytic leukaemia; ALL; blast-phase CML; intrathecal therapy of meningeal leukaemia

CML, head and neck cancer with radiotherapy, melanoma, ovarian cancer (historic labelling)

Polycythaemia vera; chronic myeloid leukaemia refractory to busulfan (historic label)

Nowell and Hungerford describe a minute chromosome in CML: the first consistent chromosomal abnormality in a human cancer.

Palliative treatment of chronic myelogenous leukaemia (Myleran tablets)