Monitoring response to treatment in CML

During and after treatment for chronic myeloid leukaemia (CML), you have regular blood tests to monitor your response. These tests:

• Check if your blood cell counts have returned to normal levels. This is done using a test called a full blood count. It is sometimes called your haematological response.
• Measure the amount of the BCR-ABL1 gene in your blood. This is done using a test called PCR. It is called your molecular response.

You also have regular appointments to check how you are feeling. This includes any symptoms or side effects you’re getting and any emotional or mental health concerns you have.

If you have any serious or worrying symptoms, you do not have to wait for your next appointment. Your haematology team should give you details of who to contact. This may be a Clinical Nurse Specialist (CNS), if one is available in your area.

Molecular response (MR) is the amount of BCR-ABL1 gene in your blood. It is a good indicator of how much leukaemia is left in your body. It is measured using a test called PCR. This test is very sensitive so it can detect extremely low levels of leukaemia in your body.

What do molecular response results mean?

The results of your PCR tests are written as a percentage or as an MR number. They can be difficult to understand.

• MR1: Less than 1 in 10 white blood cells (10%) has the BCR-ABL1 gene. If your treatment is working well, you should reach MR1 within 3 months of starting treatment.
• MR2: Less than 1 in 100 white blood cells (1%) has the BCR-ABL1 gene. If your treatment is working well, you should reach MR2 within 6 months of starting treatment.
• MR3: Less than 1 in 1,000 white blood cells (0.1%) has the BCR-ABL1 gene. This is sometimes called a major molecular response (MMR). If your treatment is working well, you should reach MR3 within 12 months of starting treatment.
• MR4: Less than 1 in 10,000 white blood cells (0.01%) has the BCR-ABL1 gene. This is sometimes called a deep molecular response (DMR). If you reach and maintain a deep molecular response, you might eventually be able to stop treatment.
• MR5: Less than 1 in 100,000 white blood cells (0.001%) has the BCR-ABL1 gene. This is also called a deep molecular response (DMR). If you reach and maintain a deep molecular response, you might eventually be able to stop treatment.
• Levels below MR5 cannot usually be detected. This is called a complete molecular response.

We have a separate factsheet about molecular response.

If you’re not sure what your results mean, ask your haematology team to explain.

Why is molecular response important?

Your molecular response can be used to detect any difficulties in treatment early on. It is also an essential part of safe monitoring if you can stop treatment.

• Some people can have a slower response to treatment and may not necessarily reach MR3 after 12 months. If you do not reach these milestones, your haematology team will talk to you about your options. They might suggest changing your treatment. This may allow you to reach a deeper response.
• If you respond to treatment at first but your level of BCR-ABL1 starts to go back up, your haematology team will talk to you about your treatment options. They may suggest increasing your dose or changing to a different treatment.

Sources we used to develop this information

Annunziata M, Bonifacio M, Breccia M, Castagnetti F, Gozzini A, Iurlo A, et al. Current Strategies and Future Directions to Achieve Deep Molecular Response and Treatment-Free Remission in Chronic Myeloid Leukemia. Front Oncol 2020;10:883.

Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. Journal of clinical oncology. 2009 Dec 12;27(35):6041.

Bonifacio M, Stagno F, Scaffidi L, Krampera M, Di Raimondo F. Management of chronic myeloid leukaemia in advanced phase. Front Oncol 2019;9: Art 1132.

Du Z, Lovly CM. Mechanisms of receptor tyrosine kinase activation in cancer. Mol Cancer 2018;17(1):58.

Garcia-Gutierrez V, Hernandez-Boluda JC. Tyrosine kinase inhibitors available for chronic myeloid leukaemia: Efficacy and safety. Front Oncol 2019;9:Art 603.

Healey MA, Allendorf DJ, Borate U, Madan A. CNS Involvement in a Patient with Chronic Myeloid Leukemia. Case Rep Hematol 2021;2021:8891376.

Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 2020;34(4):966-984.

Hochhaus A, Saussele S, Rosti G, Mahon FX, Janssen JJWM, Hjorth-Hansen H, et al; ESMO Guidelines Committee. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28(suppl_4):iv41-iv51.

Hughes TP, Mauro MJ, Cortes JE, Minami H, Rea D, DeAngelo DJ, et al. Asciminib in chronic myeloid leukaemia after ABL kinase inhibitor failure. N Engl J Med 2019; 381:2315-2326.

Incyte Biosciences UK Ltd. Ponatinib 15 mg tablets. Summary of Product Characteristics. July 2022. Available at: https://www.medicines.org.uk/emc/product/1212/smpc [Last accessed 9/11/23]

Jabbour E, Kantarjian H, Cortes J. Use of second- and third-generation tyrosine kinase inhibitors in the treatment of chronic myeloid leukaemia: an evolving treatment paradigm. Clin Lymphoma Myeloma Leuk 2015;15(6):323-334.

Janssen L, Blijlevens NMA, Drissen MMCM, Bakker EA, Nuijten MAH, Janssen JJWM, et al. Fatigue in chronic myeloid leukemia patients on tyrosine kinase inhibitor therapy: predictors and the relationship with physical activity. Haematologica 2021;106(7):1876-1882.

Medac. Hydroxycarbamide 500 mg capsules. Summary of Product Characteristics. February 2023. Available at: https://www.medicines.org.uk/emc/product/254/smpc [Last accessed 07/11/2023]

Mylan. Dasatinib 100 mg tablet. Summary of Product Characteristics. 25 July 2023. Available at: https://www.medicines.org.uk/emc/product/14399/smpc. [Last accessed: 9/11/23]

National Institute for Health and Care Excellence (NICE). Asciminib for treating chronic myeloid leukaemia after 2 or more tyrosine kinase inhibitors. Technology appraisal guidance [TA813]. Published: 03 August 2022. Available at:  https://www.nice.org.uk/guidance/ta813

National Institute for Health and Care Excellence (NICE). Bosutinib for previously treated chronic myeloid leukaemia. Technology appraisal guidance [TA401] Published: 24 August 2016. Available at: https://www.nice.org.uk/guidance/ta401

National Institute for Health and Care Excellence (NICE). Dasatinib, nilotinib and high-dose imatinib for treating imatinib-resistant or intolerant chronic myeloid leukaemia. Technology appraisal guidance [TA425]. Published: 21 December 2016. Available at: https://www.nice.org.uk/guidance/ta425

National Institute for Health and Care Excellence (NICE). Dasatinib, nilotinib and imatinib for untreated chronic myeloid leukaemia. Technology appraisal guidance [TA426] Published: 21 December 2016. Available at: https://www.nice.org.uk/guidance/ta426

National Institute for Health and Care Excellence (NICE). Ponatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia. Technology appraisal guidance [TA451] Published: 28 June 2017. Available at: https://www.nice.org.uk/guidance/ta451 [Last accessed 9/11/23]

Novartis Pharmaceuticals. Imatinib 100 mg tablets. Summary of Product Characteristics. October 2023. Available at: https://www.medicines.org.uk/emc/product/7779/smpc [Last accessed 9/11/23]

Novartis Pharmaceuticals. Nilotinib 150 mg capsules. Summary of Product Characteristics. October 2023. Available at: https://www.medicines.org.uk/emc/product/5852/smpc [Last accessed 9/11/23]]

Pfizer Limited. Bosutinib 100 mg tablet. Summary of Product Characteristics. 15 May 2023. Available at: https://www.medicines.org.uk/emc/product/3147/smpc. [Last accessed: 9/11/23]

Radivoyevitch T, Jankovic GM, Tiu RV, Saunthararajah Y, Jackson RC, Hlatky LR, et al. Sex differences in the incidence of chronic myeloid leukemia. Radiat Environ Biophys 2014;53(1):55-63.

Saglio G, Gale RP. Prospects for achieving treatment-free remission in chronic myeloid leukaemia. Br J Haematol 2020;190(3):318-327.

Smith G, Apperley J, Milojkovic D, Cross NCP, Foroni L, Byrne J, et al; British Society for Haematology. A British Society for Haematology Guideline on the diagnosis and management of chronic myeloid leukaemia. Br J Haematol 2020;191(2):171-193. Soverini S, Mancini M, Bavaro L, Cavo M, Martinelli G. Chronic myeloid leukaemia: the paradigm of targeting oncogenic tyrosine kinase signalling and counteracting resistance for successful cancer therapy. Mol Cancer 2018;17(1):49

Swerdlow SH, Campo E, Harris NL, Jaffa ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017.

Westerweel PE, Te Boekhorst PAW, Levin MD, Cornelissen JJ. New approaches and treatment combinations for the management of chronic myeloid leukaemia. Front Oncol 2019;9: Art 665.