Understanding chronic myeloid

leukemia (CML)
Chronic myeloid leukemia (CML) is a type of cancer that starts in the
blood-forming cells of the bone marrow and invades the blood1.

There are three phases of CML: chronic-phase, accelerated-phase, and blast-phase.

In most patients, CML is diagnosed in the early, chronic phase, and if properly treated may
remain in this phase without progressing to a more advanced phase2.

CML statistics
1.2 to 1.5 million people are currently living with CML worldwide3

About 15% of all leukemia cases are CML4

The average age at diagnosis for CML is 64 years; it is rarely seen in children4

CML is slightly more common in men5

The Ph chromosome
CML is caused by a genetic mutation called the Philadelphia (Ph) chromosome – a
rearrangement in the genetic material between chromosomes 9 and 226.

The Ph chromosome carries a defective gene called BCR-ABL, which produces

a protein of the same name. The protein triggers bone marrow to keep making
abnormal white blood cells. When the Ph chromosome is present, CML is classified
as Philadelphia chromosome-positive (Ph+)6.

95% of CML cases are classified as Ph+ CML7.

Chromosomal rearrangement

Ph Chromosome

BCR-ABL Gene
BCR BCR
ABL
ABL

Symptoms of CML
Many patients with CML do not show symptoms when diagnosed, and the disease
is often found when a doctor orders a blood test for unrelated health problems, or
during a routine checkup8.

When symptoms of CML do develop, they may include9:

Fatigue

Weight loss

Bone pain

Fever

Pain below the ribs from an enlarged spleen

Monitoring, management, and milestones

Routine monitoring of BCR-ABL levels through a sensitive blood polymerase
chain reaction (PCR) test can detect early and deep response to treatment and is
fundamental to the management of Ph+ CML10.

This is a simplified way to understand CML treatment milestones. Think of the dots
shown in the body as the amount of leukemic cells in the blood. With each treatment
milestone, the amount of leukemia in the body is reduced.

AT DIAGNOSIS EARLY MOLECULAR

The level of BCR-ABL in the RESPONSE (EMR)
body is different for every The level of BCR-ABL in the body
patient at diagnosis. The is ≤10% on the IS11
values are reported on the
International Scale (IS) so that
they can be compared with
other patients 11

COMPLETE MAJOR MOLECULAR

CYTOGENETIC RESPONSE (MMR)
RESPONSE (CCYR) The level of BCR-ABL in the body is
The level of BCR-ABL in ≤0.1% on the IS11*
the body is expected to
correspond with ≤1%
on the IS11*

Patients and their health care providers should work together to establish proper
treatment goals; with regular monitoring and assessment of tolerability, treatment may
need to be adjusted.

Treatment and management of CML

The introduction of tyrosine kinase inhibitor (TKI)
therapy more than 20 years ago helped transform
CML into a chronic disease for many patients, opening
possibilities to achieve deeper and stable responses12,13.

Most TKIs target the ATP binding site of the BCR-ABL gene, blocking this gene’s ability to send
signals to produce the leukemic cells14.

Need for additional advances

Despite the significant advancements in CML care over the last few decades, many
patients remain at risk of disease progression, and the sequential use of currently
available TKIs is associated with treatment resistance and/or intolerance, resulting in
increased failure rates in later lines15-19.

Some patients with CML develop mutations that cause resistance to TKI therapy,
including the T315I mutation, which confers resistance to most available TKIs. As a
result, patients harboring this mutation have limited treatment options20,21.

In patients with later-line (≥ third-line)

CML, approximately 55% reported
intolerance to a previous TKI*22.

There remains a significant unmet need for novel treatment options for patients
with Ph+ CML who do not respond adequately to available therapies.

*Data from an analysis of studies where patients were treated with 2 prior TKIs

References:
1. American Cancer Society. What Is Chronic Myeloid Leukemia? 2021. Available at https://www.cancer.org/cancer/chronic-myeloid-leukemia/
about/what-is-cml.html. 2. American Cancer Society. Phases of Chronic Myeloid Leukemia. 2021. Available at https://www.cancer.org/cancer/
chronic-myeloid-leukemia/detection-diagnosis-staging/staging.html. 3. Experts in Chronic Myeloid Leukemia. The price of drugs for chronic
myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. Blood.
2013;121(22):4439-4442. doi:10.1182/blood-2013-03-490003 4. American Cancer Society. Key Statistics for Chronic Myeloid Leukemia. 2021.
https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/statistics.html. 5. American Cancer Society. Risk Factors for Chronic Myeloid
Leukemia. 2021. https://www.cancer.org/cancer/chronic-myeloid-leukemia/causes-risks-prevention/risk-factors.html 6. National Cancer
Institute. Chronic Myelogenous Leukemia Treatment (PDQ®)–Patient Version. 2021. Available at https://www.cancer.gov/types/leukemia/patient/
cml-treatment-pdq. 7. Kang ZJ, Liu YF, Xu LZ, et al. The Philadelphia chromosome in leukemogenesis. Chin J Cancer. 2016;35:48. Published 2016
May 27. doi:10.1186/s40880-016-0108-0 8. American Cancer Society. Tests for Chronic Myeloid Leukemia. 2021. Available at https://www.cancer.
org/cancer/chronic-myeloid-leukemia/detection-diagnosis-staging/how-diagnosed.html. 9. American Cancer Society. Signs and Symptoms
of Chronic Myeloid Leukemia. 2021. Available at https://www.cancer.org/cancer/chronic-myeloid-leukemia/detection-diagnosis-staging/signs-
symptoms.html. 10. Soverini S, De Benedittis C, Mancini M, Martinelli G. Best Practices in Chronic Myeloid Leukemia Monitoring and Management.
Oncologist. 2016;21(5):626-633. doi:10.1634/theoncologist.2015-0337 11. Hehlmann R, Müller MC, Lauseker M, et al. Journal of Clinical Oncology
: Official Journal of the American Society of Clinical Oncology. 2014 Feb;32(5):415-423. DOI: 10.1200/jco.2013.49.9020. 12. National Institutes of
Health. Fighting Cancer: Ushering in a new era of molecular medicine. Available at https://www.nih.gov/sites/default/files/about-nih/impact/
fighting-cancer-case-study.pdf. 13. Rossari, F., Minutolo, F. & Orciuolo, E. Past, present, and future of Bcr-Abl inhibitors: from chemical development
to clinical efficacy. J Hematol Oncol 11, 84 (2018). https://doi.org/10.1186/s13045-018-0624-2. 14. Garg RJ, et al. Blood. 2009;114(20):4361-4368.
15. Ibrahim AR, et al. Efficacy of tyrosine kinase inhibitors (TKIs) as third-line therapy in patients with chronic myeloid leukemia in chronic phase
who have failed 2 prior lines of TKI therapy. Blood. 2010 Dec 16;116(25):5497-500. doi: 10.1182/blood-2010-06-291922. Epub 2010 Sep 10. PMID:
20833982; PMCID: PMC6143154. 16. Gambacorti-Passerini C, et al. Am J Hematol. 2014 Jul;89(7):732-42. doi: 10.1002/ajh.23728. Epub 2014 Apr
28. PMID: 24711212; PMCID: PMC4173127. 17. Shah NP, et al. Haematologica. 2010 Feb;95(2):232-40. doi: 10.3324/haematol.2009.011452. PMID:
20139391; PMCID: PMC2817025. 18. Kantarjian HM, et al. Blood. 2010;117(4):1141-1145. doi:10.1182/blood-2010-03-277152. 19. Hochhaus A, et al.
European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34:966-984 20. Jabbour E, Kantarjian H.
Chronic myeloid leukemia: 2018 update on diagnosis, therapy and monitoring. Am J Hematol. 2018 Mar;93(3):442-459. doi: 10.1002/ajh.25011. PMID:
29411417. 21. Fabian MA, Biggs WH III, Treiber DK, et al. Nat Biotechnol. 2005;23(3):329-336. 22. Giles FJ, et al. Leukemia. 2010; 24(7):1299–1301.

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