What is Chronic Myeloid Leukemia (CML)?
A disease of the white blood cells found in the bone marrow that results when 2 chromosomes trade small sections of their DNA forming what is known as the “Philadelphia Chromosome.” When this happens within a white blood cell, it may grow and divide without being able to stop.
CML is a relatively rare condition and represents about 10% of diagnosed leukemias. CML is not thought to be an inherited disorder and most of the time, the cause is unknown. The average age at diagnosis is about 65 years old.
CML can present in one of three phases: Chronic Phase, Accelerated Phase, or Blast Crisis
Without treatment, CML may evolve over time causing aggressive disease. This may lead to symptoms such as weight loss, abdominal discomfort, decreased appetite, fever, bruising or bleeding, among others. The stage of CML can vary at diagnosis and throughout treatment. The effectiveness of the treatment may depend upon the phase of CML at diagnosis.
NOTE: Treatment Options listed below are not all-inclusive. Other treatments may be available. ChemoExperts provides drug information and does not recommend any one treatment over another. Only your Doctor can choose which therapy is appropriate for you.
What is Chronic Phase?
When a patient with CML has a bone marrow biopsy that shows less than 10% blasts, they are said to be in chronic phase. Patients in chronic phase have few or no symptoms from CML.
What is Accelerated Phase?
When a patient with CML has a bone marrow biopsy that shows between than 11 – 20% blasts, they are said to be in accelerated phase. Patients with accelerated phase usually have symptoms such as poor appetite, weight loss, an enlarged spleen, or fever.
What is Blast Phase?
When a patient with CML has a bone marrow biopsy that shows more than 20% blasts, they are said to be in blast phase, or blast crisis. Patients with blast phase usually have symptoms similar to acute leukemia such as: easy bruising or bleeding, fever, poor appetite, weight loss, or an enlarged spleen.
Clinical Studies
If you are interested in reading the clinical trial results, please click on the references below:
1) Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia-chromosome positive leukemias. N Engl J Med. 2013;369:1783-1796.
2) Daily Med: Ponatinib Drug Label Information
What is BCR/ABL?
A gene mutation within CML cells. The percent of cells that have the BCR/ABL mutation goes down by taking ponatinib therapy. The goal is that the percentage will become undetectable. This happens in the many patients and is known as a complete molecular response, or 0.000%. At diagnosis, the BCR/ABL % is often very high, sometimes exceeding 100%. This is because the test is based upon the average BCR/ABL% from patients in one of the earliest clinical studies with imatinib. Having a BCR/ABL% greater than 100% at diagnosis does not usually affect the response to ponatinib.
Responding to Ponatinib?
The optimal response to ponatinib depends upon how long you have been taking it for. Ultimately, the goal is an undetectable BCR/ABL%, or 0.0000%, but a level less 1% usually predicts long-term survival as well. Patients who have a BCR/ABL of 10% or more after 3 months of ponatinib (without missing doses) may need to switch therapy to another medication that treats CML.
Goal BCR/ABL% (International Scale, IS) while taking Ponatinib therapy:
- Newly Diagnosed (No Ponatinib therapy): Variable [~80 - more than 100%]
- Complete Hematologic Response (CHR): Less than 10%
- Complete Cytogenetic Response (CCyR): Less than 1%
- Major Molecular Response (MMR): Less than 0.1%
- Complete Molecular Response (CMR): 0.0000%
What are diuretics?
Diuretics are medicines used to make people urinate. They are usually taken to help get rid of excess water that the body is holding onto. Excess water weight usually appears as swelling in the extremities such as arms, legs, or feet. It can occur in other areas such as in the lungs or around the eyes.
What is Tumor Lysis Syndrome?
Tumor lysis syndrome occurs when many cancer cells die quickly and release their contents into the bloodstream. Many times the body has the ability to flush these substances out through the kidneys or metabolize them via the liver. However, sometimes the body needs medicines to help eliminate these substances and to prevent organ damage.
What is a CBC?
A Complete Blood Count (CBC) is a frequently ordered blood test that tells clinicians the status of your: 1) White blood cell count, 2) Hemoglobin, and 3) Platelet count at the time the test was taken.
Common uses:
1) White blood cell count (WBC): is used to determine infection risk, or response to chemotherapy. Certain chemotherapy agents may harm our good infection-fighting cells. Sometimes chemotherapy may need to be delayed to allow these cells to recover.
2) Hemoglobin: is used to determine if someone is anemic. Anytime the hemoglobin is below 12 g/dL, the person is said to be anemic. Red blood cell transfusions, and sometimes iron can be given to restore the hemoglobin level, but anemia treatment should always aim at treating the underlying cause or condition.
3) Platelet count: is used to determine if the risk of bleeding is increased or if a platelet transfusion is required to prevent bleeding. Certain medications that increase bleeding risk, such as: aspirin, certain chemotherapy agents, and blood thinners, may need to be stopped temporarily until the platelet count is within a safe range.
What is a CMP?
A Comprehensive Metabolic Panel (CMP) is a frequently ordered blood test that tells clinicians the status of your: 1) Electrolytes & Acid/Base status, 2) Kidney function, 3) Liver function, 4) Blood sugar, and 5) Calcium at the time the test was taken. It is commonly used to monitor liver and kidney function when beginning new medications such as chemotherapy. A total of 14 tests are run simultaneously and are shown below.
Electrolytes & Acid/Base status:
1) Sodium, 2) Potassium, 3) Carbon dioxide, 4) Chloride
Kidney Function:
5) BUN (blood urea nitrogen), 6) Serum creatinine (Scr)
Liver Function:
7) AST, 8) ALT, 9) Total bilirubin, 10) Alk Phos, 11) Albumin, 12) Total protein
Blood sugar:
13) Serum glucose
Calcium:
14) Serum calcium
What does "cure" mean?
The word “cure” means there are no cancer cells left in the body and cancer will never come back. Depending on the cancer type and stage, this may be the true goal of therapy. However, it is very difficult to prove all cancer cells are gone. Even though images, like X-rays and MRI’s, and blood tests may not show any signs of cancer, there can be a small amount of cancer cells still left in the body. Because of this, doctors use the word “remission” more often. This means there are no signs or symptoms of cancer. Patients in remission are followed closely for any signs of cancer returning. Sometimes, more chemotherapy may be given while in remission to prevent the cancer from coming back.
Doctors usually do not consider a patient “cured” until the chance of cancer returning is extremely low. If cancer does return, it usually happens within 5 years of having a remission. Because of this, doctors do not consider a patient cured unless the cancer has not come back within 5 years of remission. The five-year cutoff does not apply to all cancers.
What is the "Ariad Pass" Program?
The makers of ponatinib, Ariad pharmaceuticals, provide a service known as the "Ariad Pass" program. Healthcare providers use this website to send in prescriptions for ponatinib. Once received, Biologics pharmacy works with patients' insurance and patient assistance foundations to dispense ponatinib at the lowest cost to patients.
When the medication is approved, Biologics pharmacy will contact you for counseling, to collect a co-pay (if any), to answer questions, and to verify your shipping address. Addiitonally, Biologics pharmacy may contact you before each refill to verify that your dose and shipping address have not changed, in addition to asking if you have side effects.
Click on our link if you are a healthcare provider wishing to write a prescription for ponatinib.
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