Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) and Chronic Myeloid Leukemia (CML) are two distinct yet related forms of cancer that arise from genetic mutations involving the Philadelphia chromosome. This chromosomal abnormality, caused by a translocation between chromosomes 9 and 22, which leads to the formation of the BCR-ABL fusion gene. Gene translocation happens when piece of a chromosome breaks off and attaches to another chromosome This is responsible for the uncontrolled growth of myeloid cancerous cells. 1
CML is a slower-progressing disease while Ph+ ALL tends to be more aggressive, but the advent of targeted therapies, particularly with the introduction of ICLUSIG, has redefined the landscape of care, offering hope to patients.
Let's explore these conditions, their symptoms, diagnosis, and management, and the key role of ICLUSIG in improving treatment prognosis. 2
Common Characteristic of Ph+ALL: 1
- -Age Groups Affected: Can occur in both children and adults but is more common in adults.
- -Diagnosis: Diagnosis is usually confirmed through bone marrow biopsy, cytogenetic analysis to identify the Philadelphia chromosome, and other blood tests.
- -Treatment: intensive chemotherapy, targeted therapy with tyrosine kinase inhibitors (such as imatinib), and may include stem cell transplantation in eligible patients.
Ph+ ALL is associated with a poorer prognosis compared to other types of acute lymphoblastic leukemia. 1
Management: Management of Ph+ ALL often involves participation in clinical trials exploring new therapies, given its aggressive nature and the involvement of specific genetic mutations.
Common characteristics of CML: 2
Phases: CML progresses through three phases:
- -Chronic: The initial phase, where patients may experience few or mild symptoms. This phase can last for several years, hence described as chronic.
- -Accelerated: A transitional phase where the disease starts taking up a more aggressive shape, with an increase in symptoms and laboratory findings indicating progression.
- -Blast Crisis: The most aggressive stage, with close resemblance to acute leukemia, where there is a significant increase in immature cells in the blood and bone marrow.
Diagnosis: Certain blood tests, bone marrow biopsy, and cytogenetic analysis to identify the Philadelphia chromosome.
Management: The primary treatment for CML is targeted therapy with tyrosine kinase inhibitors (TKIs), such as imatinib. These drugs specifically target the BCR-ABL protein and can effectively control the disease. In cases where CML refracts to treatment or progresses to advanced phases, options may include chemotherapy, stem cell transplantation, or newer targeted therapies. 1, 2
Living with Chronic Myeloid Leukemia (CML) and Ph+ ALL can present numerous challenges and struggles, affecting physical health and emotional well-being. Patients battling these diseases often have to suffer from the following things: 3
Physical Symptoms:
- -Fatigue: Constant tiredness can impact daily activities and quality of life.
- -Pain and Discomfort: Some patients may experience bone pain or discomfort due to an enlarged spleen.
- -Side Effects of Treatment: Medications, particularly tyrosine kinase inhibitors (TKIs), can cause side effects like nausea, diarrhea, skin rashes, and more.
-Emotional and Psychological Struggles: The diagnosis of such a severe illness can lead to feelings of worry about the future, treatment effectiveness, and the possibility of disease progression
-Social Isolation: These diseases can affect relationships with family and friends, leading to feelings of isolation or misunderstanding from others who may not fully understand the illnesses. Patients may need to adjust their social activities and outings due to fatigue, their treatment side effects, as well as the increased risk of infections.
-Navigating Healthcare: Managing medication regimens, monitoring of diseases status and potential side effects requires careful coordination with doctors. Patients often struggle with understanding medical jargon, lab results, and treatment options, which can lead to confusion and a lot of frustration.
-Adherence to Treatment: Sticking to a routine of taking medications as prescribed is crucial, but side effects can lead to missed doses or non-adherence. Some side-effects make it harder to do basic things which can be demotivating, continuing medications that cause discomfort is challenging and can test one's will-power.
Coping Strategies:
-Seek Support: Joining support groups, talking to mental health professionals, or connecting with other patients can help alleviate feelings of isolation.
-Self-education: Learn about your condition to make informed decisions regarding your treatment and management.
-Self-Care: Regular exercise, a healthy diet, and mindfulness practices may improve overall well-being and help manage symptoms as well as stress that inevitably comes with overcoming cancer.
-Monitoring and Prognosis: Regular monitoring of blood counts and genetic tests is crucial for assessing treatment response and disease progression. The prognosis for patients with CML and Ph+ALL has improved significantly with the advent of targeted therapies, Tyrosine Kinase Inhibitors such as ICLUSIG , many patients can achieve long-term remission.
Why tyrosine kinase inhibitors? 4
Abnormal activation of certain tyrosine kinases is often implicated in the pathogenesis of this type of cancer.
Tyrosine kinases play a key role in the signalling pathways of the body that regulate cell growth, and their dysregulation, through mutations or fusion genes like BCR-ABL1, that lead to Ph+ALL Leukemia and CML.
ICLUSIG is a tyrosine kinase inhibitor prescription medicine used to treat adults who have,5
Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
- -In combination with chemotherapy in newly diagnosed Ph+ ALL
- -Alone in adults with Ph+ ALL who cannot receive any other kinase inhibitor medicines or who have a specific type of abnormal gene (T315I-positive) Ph+ ALL 5
Chronic Myeloid Leukemia (CML)
- -Chronic phase CML who did not tolerate or no longer benefit from treatment with at least 2 regularly prescribed tyrosine kinase inhibitor medicines
- -Accelerated phase or blast phase CML who cannot receive any other kinase inhibitor medicines.
- -A specific type of abnormal gene (T315I-positive) chronic phase, accelerated phase, or blast phase CML 6
ICLUSIG is not used to treat people with newly diagnosed chronic phase CML. 5
It is unknown if ICLUSIG is safe and effective for pediatric use.5, 6
ICLUSIG in combination with chemotherapy in newly diagnosed adult patients with Ph+ ALL was approved based on patient responses at 3 months of therapy. There is an ongoing study to confirm results.7
Iclusig (ponatinib) is considered a life-saving medicine, especially for patients with certain types of leukemia. Lets understand why:
Benefits of ICLUSIG 6
-Effective for Drug-Resistant Cancers: Iclusig is used primarily for treating chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL), particularly when these cancers are resistant or intolerant to other treatments like imatinib (Gleevec). This makes it a critical option for patients who no longer respond to standard therapies.
-Targets Specific Mutations: Iclusig is designed to target the BCR-ABL fusion protein that is responsible for the growth of leukemic cells. It works effectively even against the T315I mutation, a mutation that many other tyrosine kinase inhibitors (TKIs) cannot treat.
-Prevents Disease Progression: By inhibiting cancer cell proliferation, Iclusig can slow or stop the progression of leukemia, improving patients' survival rates and quality of life.
-FDA-Approved for Severe Cases: Iclusig is approved for patients with CML in chronic, accelerated, or blast phases, as well as those with Philadelphia chromosome-positive ALL, which are conditions with few effective treatment options. For many, it represents a last-line treatment that can help manage or control the disease.
-Improves Long-Term Prognosis: When used appropriately, Iclusig has been shown to provide long-term remission for some patients, allowing them to live longer and with better health outcomes compared to previous options.
Despite its life-saving potential, it's essential to note that Iclusig can have serious side effects, so it must be carefully managed under the guidance of a healthcare provider.
Side effects:
ICLUSIG (ponatinib) can cause several adverse effects, some of which can be serious. Common side effects include:5
- -Blood Clots: ICLUSIG can increase the risk of blood clots, which may lead to heart attacks, strokes, or other severe complications.
- -Heart Problems: It can cause heart failure, irregular heartbeats, or other heart-related issues.
- -Liver Problems: Liver toxicity, including elevated liver enzymes or liver damage
- -Low Blood Counts: This can lead to anemia (low red blood cells), thrombocytopenia (low platelets), or neutropenia (low white blood cells).
- -Fatigue and headaches: Feeling unusually tired or weak, some people may experience headaches.
- -Skin rashes may occur.
- -Gastrointestinal Issues: Nausea, diarrhea, and abdominal pain can be side effects.
Less common but more severe side effects include pancreatitis, bleeding, and severe allergic reactions. It’s important to regularly monitor for these side effects while on ICLUSIG treatment. 5
The When, How and Where of ICLUSIG usage & approval:
-When: Iclusig was first approved by the U.S. Food and Drug Administration (FDA) in December 2012. It was granted approval under the FDA’s accelerated approval pathway based on early clinical data showing its effectiveness in treating resistant or refractory CML and Ph+ ALL.8
-Where: The drug was approved for use in the United States. It is also approved in various other countries around the world like the European Union, Australia, Switzerland, Israel, Canada, Japan and several other countries throughout Asia, though approval timelines vary by region.9
-How: The approval was based on clinical trials that demonstrated the drug's ability to effectively target and inhibit the BCR-ABL1 tyrosine kinase, a key driver in the development of CML and Ph+ ALL. The presence of the T315I mutation in the BCR-ABL gene makes some leukemias resistant to other tyrosine kinase inhibitors, but Iclusig is effective against this mutation.5
ICLUSIG is used particularly in patients who have failed to achieve satisfactory results or are intolerant to other treatments, such as imatinib or dasatinib, and in those with the T315I mutation, which confers resistance to other tyrosine kinase inhibitors.5
Conclusion
ICLUSIG is a targeted therapy that’s revolutionized the treatment of Philadelphia Chromosome-Positive Leukemias. Where traditional treatments have faltered, Iclusig’s ability to target specific mutations, such as the T315I mutation provides a critical treatment option for patients with CML and Ph+ ALL.
While its potential risks require careful management, research continues to evolve. We currently have real-life stories of people diagnosed with cancer who got ICLUSIG therapy and have since then achieved and maintained clinical remission of cancer.7 Every body reacts differently and, it’s essential for patients and doctors to stay informed about treatments to maximize better prognosis and improve quality of life.
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Note:
The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.
References:
1: https://pmc.ncbi.nlm.nih.gov/articles/PMC4199301/#:~:text=The%20Philadelphia%20chromosome%20(Ph)%20is,of%2045%20%25%20to%2090%20%25.
2: https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/chronic-myeloid-leukaemia/#:~:text=Chronic%20myeloid%20leukaemia%20(CML)%20is,It%20has%20three%20phases:
3: https://www.msdmanuals.com/home/blood-disorders/leukemias/chronic-myeloid-leukemia-cml
4: https://www.cancerresearchuk.org/about-cancer/chronic-myeloid-leukaemia-cml/treatment/targeted-drugs#:~:text=The%20most%20common%20treatment%20for,%2C%20bosutinib%2C%20dasatinib%20and%20nilotinib.
5: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/203469s037lbl.pdf
6: https://www.ema.europa.eu/en/medicines/human/EPAR/iclusig#:~:text=Iclusig%20was%20shown%20to%20be,dose%20reduction%20or%20dose%20delay.
7: https://www.iclusig.com/
8: https://www.drugs.com/history/iclusig.html
9: https://investor.incyte.com/news-releases/news-release-details/incyte-and-ariad-announce-agreement-incyte-acquire-ariads#:~:text=Terms%20of%20the%20Agreements&text=In%20addition%20to%20the%20SPA,each%20of%202016%20and%202017.
