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Blood Cancer

Blood Cancer

Chronic Myeloid Leukemia

 

Chronic Myeloid Leukemia (CML) is one of the most common hematologic malignancies, accounting for 15% of all leukemias in adults.1 Primarily affecting adults who are older than 64 years of age, CML is rarely seen in children.2 Current therapies for CML make this a highly treatable disease with a survival rate of greater than 90% on effective tyrosine kinase inhibitor therapy.3

Explore the Biology of CML

CML Statistics

Europe

  • Estimated Prevalence = 10-12 per 100,000 inhabitants24
  • Steady increase in CML patients is due to dramatic improvements in survival24
  • Estimated New CML Cases per Year = 6,3704

 

United States

  • Prevalence is predicted to double from 2010 – 203014
  • Predicted New CML Cases in 2019 = 8,9902

 

Global

  • Incidence Rate in Africa = 0.46
  • Incidence Rate in Latin America = 0.76
  • Incidence Rate in Asia Pacific = 0.7 - 1.26

CML Biology

As a type of blood cancer, Chronic Myeloid Leukemia (CML) affects immature myeloid cells in the bone marrow, impeding their normal differentiation into red blood cells, platelets, and some white blood cell types.4

While research continues to build our understanding of how CML is initially triggered, we do know that a genetic, reciprocal translocation between chromosomes 9 and 22 leads to the formation of a truncated chromosome 22, termed “the Philadelphia chromosome”. This altered BCR-ABL1 gene holds the blueprints for the development of dysregulated tyrosine kinase proteins responsible for driving the rapid growth of CML cells.5

Tyrosine kinases are enzymes that play a key role in the growth, differentiation, metabolism and apoptosis of normal cells. Particularly responsible for preventing the unchecked growth of cells, the dysregulated tyrosine kinase produced from a BCR-ABL translocation results in the malfunctioning of signaling pathways.

This leads to uncontrolled growth of immature myeloid cells in the bone marrow that can crowd out other blood cell types and spill into the surrounding blood stream interfering with normal hematopoiesis.6

This illustration details the formation of the Philadelphia chromosome. 20

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CML Treatment

CML Treatment

>90% of CML patients survive more than 5 years after their initial diagnosis22

In the last 15 years we have seen extraordinary breakthroughs in the management of Chronic Myeloid Leukemia (CML) with the introduction of tyrosine kinase inhibitors (TKIs). TKIs are a class of drugs that block the function of the abnormal tyrosine kinase protein, stopping the excessive build-up of immature blood cells.

The efficacy of TKI therapy is often assessed with hematologic and molecular testing which is measured alongside time-bound milestones, helping to inform treatment decisions.7

Molecular testing is performed using real-time quantitative polymerase chain reaction (RT-qPCR) to determine molecular response throughout CML treatment. These results are standardized against the International Scale to minimize variability and to quantify the level of BCR-ABL1 transcripts present in CML patients.7

 

 

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Fast CML Monitoring

Fast CML Monitoring

61% of CML patients who have agreed with their doctor to discontinue treatment suffer a molecular
relapse7

The recommended method for regular molecular monitoring of Chronic Myeloid Leukemia (CML) is real-time quantitative polymerase chain reaction (RT-qPCR). The monitoring test should report on the International Scale (%IS) and be repeated several times a year.8

An estimated 40%-60% of CML patients in the chronic phase can achieve a sustained deep molecular response (DMR) for greater than 2 years through TKI treatment making them eligible for treatment discontinuation. The cessation of medication is possible with an emphasis on strict and regular CML monitoring to ensure prompt action can be taken in cases of relapse. This is considered a functional cure even though evidence of CML may remain present but at a level that is safe and stable to manage without TKI treatment.7

Of the patients who relapse, 95% of these CML patients relapse within 7 months of treatment cessation. There is a greater need for fast and sensitive molecular diagnostic testing to support timely treatment decisions.7

 

 

Diagnosis

About 50% of patients with CML diagnosed in Europe are asymptomatic.9

CML Diagnosis Perspectives

image/svg+xml Clinician View
image/svg+xml Patient View

90% of CML patients who are diagnosed are in the chronic phase, which is characterized by an elevated white blood cell count and traces of immature granulocytes in the peripheral blood10

The following tests can be used to diagnose CML:

  • Complete Blood Count (CBC)
  • Peripheral Blood Smear
  • Bone Marrow Aspiration & Biopsy
  • Cytogenic Analysis
  • Fluorescence In Situ Hybridization (FISH)9

Nowadays, with more CML patients reaching Molecular Response 4.5 (MR4.5), alternative treatment options are available to clinicians, with guidelines recommending time critical testing and increased monitoring frequency.

CML is a slow-growing disease that is not characterized by distinct symptoms

Although, some patients may report (prior to diagnosis) having experienced:

  • Bone pain
  • Fatigue 
  • Fever
  • Night sweats
  • Pain below the ribs
  • Shortness of breath
  • Weakness
  • Weight loss
Treatment

The 5-year survival rate for CML patients has dramatically increased from 31% in the 1990s to greater than 90% in 2018.22

CML Treatment Perspectives

image/svg+xml Clinician View
image/svg+xml Patient View

The introduction of the tyrosine kinase inhibitor imatinib mesylate (Gleevec®) in 2001 followed by approval of 2nd generation and 3rd generation TKIs transformed CML into a manageable blood cancer.9

Although TKIs have become standard therapy due to their ability to induce a high rate of hematologic and cytogenic responses, some patients may develop resistance. Second-generation TKIs (e.g. dasatinib, nilotinib) were developed as an alternative for those patients who develop TKI resistance. While broader TKI resistance is also possible, research continues to explore how it arises while also working to develop new agents that may help improve outcomes, such as aurora kinase inhibitors and homoharringtonine.10

During cancer treatment, both patients and clinicians want answers quickly. A survey conducted in collaboration with the French CML Patient Association uncovered a strong correlation between the anxiety levels of newly diagnosed CML patients and the length of their wait time for molecular test results.12

Survey Results:

  • 50% of newly treated patients defined their wait time as lengthy
  • 61% described their quality of life as abnormal while waiting for their test results
  • 78% of patients would like to receive their monitoring results within 48 hours12

 

Download the Patient Survey

Monitoring

By 2050, there will be approximately 181,000 people living with CML in the United States.14

CML Monitoring Perspectives

image/svg+xml Clinician View
image/svg+xml Patient View

Real-time quantitative polymerase chain reaction (RT-qPCR) testing with results reported against the International Scale (IS) is recommended by the NCCN Guidelines Version 4.2018 at the following time intervals:

  • Every 3 months following the start of treatment
  • Every 3 months for 2 years once BCR-ABL1 (IS) <1% (>0.1%-1%) is achieved
  • Every 3-6 months beyond 2 years of sustained BCR-ABL1 (IS) <1% (>0.1%-1%) response13

Only 32% of patients receive their results within 15 days or less from the time their blood was sampled. Some methods of CML monitoring offer longer than desired wait times for test results possibly leading to elevated patient anxiety and a delay in medical decisions.13

While frequent and continuous monitoring is required for CML patients in the chronic phase, not all patients will have medically documented monitoring during the first 12 months of TKI therapy. The NCCN and ELN recommendations for response monitoring may not always translate into daily clinical practice impacting treatment strategies.15