Asciminib, known by its brand name Scemblix, represents a targeted therapy for chronic myeloid leukemia (CML). This medication is specifically designed for adults with Philadelphia chromosome-positive (Ph+) CML in the chronic phase, particularly when they have not responded well to at least two prior treatments, or for those with a specific gene mutation (T315I). Unlike older tyrosine kinase inhibitors (TKIs) that bind to the ATP-binding site of the cancer-driving protein, asciminib works differently. It acts as a STAMP inhibitor, specifically targeting the ABL myristoyl pocket of the BCR-ABL1 protein, which induces an inactive conformation and reduces the protein’s activity. This distinct mechanism provides a new approach to combat resistance to other TKIs.
Common Side Effects
Asciminib can cause several common side effects, generally mild to moderate in severity. Fatigue is a common complaint. Upper respiratory tract infections, affecting the nose, throat, or sinuses, are also reported.
Gastrointestinal issues are prevalent, including nausea, stomach-area (abdominal) pain, and diarrhea. Patients might also experience muscle, bone, or joint pain, which can range from mild aches to more pronounced discomfort. Headaches and skin rash are other common occurrences, with rash sometimes appearing as redness or irritation on the skin.
Blood tests can reveal other common changes, such as decreased blood cell counts, including low white blood cells (neutropenia), low red blood cells (anemia), and low platelet counts (thrombocytopenia). Increases in certain blood enzyme levels, like lipase and amylase (pancreatic enzymes), liver enzymes (alanine aminotransferase, aspartate aminotransferase), and creatine kinase, are also observed. Additionally, changes in blood fat levels, specifically increased cholesterol and triglycerides, and elevated uric acid levels can occur.
Serious Side Effects
While less common, some asciminib side effects are serious and require immediate medical attention. Pancreatic problems, such as inflammation of the pancreas (pancreatitis), can cause severe stomach pain that may spread to the back, accompanied by nausea or vomiting. Elevations in pancreatic enzymes, lipase and amylase, are often detected through blood tests and can signal this condition.
Cardiovascular issues are another serious concern, encompassing heart attack, stroke, blood clots, blockages in arteries, heart failure, and abnormal heart rhythms. Symptoms to watch for include shortness of breath, chest pain or pressure, a feeling of rapid or irregular heartbeats, and swelling in the ankles or feet. Sudden numbness or weakness on one side of the body, vision changes, or trouble talking could indicate a stroke.
Bone marrow suppression can lead to significantly low blood cell counts, increasing the risk of infection, unusual bleeding, or easy bruising. Signs of infection like fever, chills, or a sore throat should be reported promptly. Severe skin reactions, including widespread rash, redness, or swelling of the face, lips, or tongue, along with difficulty breathing or swallowing, may also occur and warrant urgent care.
Managing Side Effects
Managing asciminib side effects involves open communication with your healthcare team. Report any new or worsening symptoms to your doctor or nurse. Always adhere strictly to the prescribed dosage and schedule; never adjust your dose or stop the medication without medical guidance.
Lifestyle adjustments can help mitigate some common issues; for instance, maintaining good hydration and making dietary changes, such as eating low-fiber, bland foods, can help with gastrointestinal problems like diarrhea. Adequate rest is beneficial for managing fatigue, and gentle exercise may also help. For muscle or joint pain, applying heat packs can provide some relief.
Healthcare providers may recommend supportive medications to alleviate symptoms like nausea or pain. In some cases, if side effects become severe or persistent, the doctor might adjust the asciminib dosage, temporarily withhold the medication, or even discontinue it.
Important Considerations and Monitoring
Medical oversight is routine during asciminib treatment to ensure patient safety and monitor for potential issues. Regular blood tests are performed to check complete blood counts, including white blood cells, red blood cells, and platelets, typically every two weeks for the first few months and then monthly. These tests also monitor levels of pancreatic enzymes (amylase and lipase), liver enzymes, lipid levels (cholesterol and triglycerides), and uric acid.
Blood pressure monitoring is also a regular assessment, as asciminib can cause hypertension. Cardiovascular assessments, including electrocardiograms (ECGs), may be conducted to evaluate heart health, especially for patients with pre-existing heart conditions.
Inform your doctor about all other medications, including over-the-counter drugs, vitamins, and herbal supplements. Asciminib can interact with certain substances like strong CYP3A4 inhibitors or grapefruit juice, potentially altering drug levels.
For women of reproductive potential, pregnancy status should be verified before starting treatment, and effective contraception must be used during therapy and for at least one week after the last dose, as asciminib can cause fetal harm. Breastfeeding is not recommended during treatment and for one week after the final dose due to the potential for serious adverse reactions in the infant.