Treatment

Once a diagnosis of chronic myeloid leukaemia is made a frank discussion of the implications is a priority.

• patient is informed that the disease reduces life expectancy but that several years of relatively normal life can be expected. In the older patient (40-50+) emphasis is placed on palliative treatment
• women who are diagnosed with CML during pregnancy should be advised that continuing to term will not affect the outcome of the pregnancy or the leukaemia.
• cryopreservation of the patient's buffy coat should be performed if autologous stem cell transplantation may be considered at a latter stage.
• young males should be offered cryopreservation of semen as infertility is a risk.

Specific palliative drug therapy includes: (1,2,3,4)

• imatinib
• recombinant alpha interferon
• hydroxyurea
• busulphan
• newer tyrosine kinase inhibitors (TKI’s) - nilotinib, dasatinib, asciminib

Transplant therapies

• autologous stem cell transplantation (SCT)
  • may prolong survival but does not reduce mortality. Long-term survival and mortality depend on age, disease status at transplant, and donor type.
  • there is no clear evidence on the benefits of autologous SCT as the initial treatment of CML
• allogeneic bone marrow transplantation
  • allogeneic stem cell transplantation (SCT) is no longer recommended as the first-line therapy in CML,
  • it is the recommended method after imatinib failure (except in high disease risk and very low transplantation risk, patient’s preference, or economic reasons
  • 30% of patients will have a HLA-matched sibling who can act as a donor
  • mortality and morbidity from this procedure may vary between 10% to 70%

Leucopheresis is used in exceptional situations to reduce the peripheral white cell count.

Recommendations for the management of CML are:

• in chronic phase
  • 1st line
    • in all patients - Imatinib 400mg daily
  • 2nd line (after imatinib)
    • higher imatinib dose
    • dasatinib or nilotinib
    • asciminib
    • allogeneic stem cell transplantation
• in accelerated and blastic phase
  • allogeneic stem cell transplantation, preceded by imatinib, dasatinib, nilotinib or asciminib

Notes:

• imatinib is recommended as first-line treatment for people with Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) in the chronic phase (5)
• imatinib is recommended as an option for the treatment of people with Philadelphia-chromosome-positive CML who initially present in the accelerated phase or with blast crisis. Additionally, imatinib is recommended as an option for people who present in the chronic phase and then progress to the accelerated phase or blast crisis if they have not received imatinib previously
• NICE defined imatinib as the first-line palliative treatment for CML whereas previously alpha interferon was used in this role
  • interferon-alpha (IFN) was considered the gold standard for drug therapy of CML, as it yielded complete cytogenetic response (CCR) in 10-25% of patients with significant survival prolongation, particularly in low risk patients usually obtaining a higher response rate
    • however, even in best responding patients, the disease still remained detectable at a molecular level, and the majority of patients eventually relapsed
    • imatinib mesylate, a selective inhibitor of the BCR/ABL TK, has revolutionized the disease management, as it induces CCR in 50-90% of chronic phase (CP) CML patients, including those resistant or refractory to IFN alpha
    • there is study evidence that indicates that patients induced into CCR by IFN treatment represent a subset with very favourable prognosis, which can significantly improve molecular response with imatinib
    • high-dose imatinib is not recommended for the treatment of chronic, accelerated or blast-crisis phase Philadelphia-chromosome-positive CML that is resistant to standard-dose imatinib (7)
• NICE have given guidance regarding the use of Azacitidine in CML (6)
• NICE (7) have stated that nilotinib is recommended for the treatment of chronic or accelerated phase Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) in adults:
  • whose CML is resistant to treatment with standard-dose imatinib or
  • who have imatinib intolerance and if the manufacturer makes nilotinib available with the discount agreed as part of the patient access scheme

In 2022 NICE recommended asciminib (a tyrosine inhibitor), as an option for treating chronic-phase Philadelphia chromosome-positive chronic myeloid leukaemia without a T315I mutation after two or more tyrosine kinase inhibitors have been tried in adults. (8)

References:

1. Smith G, Apperley J, Milojkovic D, et al. A British Society for Haematology guideline on the diagnosis and management of chronic myeloid leukaemia. Br J Haematol. 2020 Oct;191(2):171-93.
2. Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020 Apr;34(4):966-84.
3. Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(Suppl 4):iv41-51.
4. Eiring AM et al. Advances in the treatment of chronic myeloid leukemia. BMC Med. 2011 Aug 26;9:99.
5. Guidance on the use of imatinib for chronic myeloid leukaemia. NICE Technology Appraisal Guidance, October 2003 - last updated January 2016
6. NICE. Azacitidine for the treatment of myelodysplastic syndromes, chronic myelomonocytic leukaemia and acute myeloid leukaemia. NICE Technology appraisal guidance TA218. Published March 2011
7. NICE. Dasatinib, nilotinib and high-dose imatinib for treating imatinib-resistant or intolerant chronic myeloid leukaemia. NICE Technology appraisal guidance TA425. Published December 2016
8. NICE. Asciminib for treating chronic myeloid leukaemia after 2 or more tyrosine kinase inhibitors. NICE Technology appraisal guidance. Published August 2022