This article was produced in partnership with AstraZeneca.
Chronic lymphocytic leukemia (CLL) is the most prevalent form of leukemia in the Western world. Despite its ominous name, CLL typically progresses slowly over a number of years. The term ‘leukemia’ refers to the uncontrolled proliferation of white cells, which are malignant in nature. In this instance, it applies to mature type B lymphocyte cells. In Israel, roughly 450 patients are diagnosed with CLL each year, with the median age of diagnosis being around 70. CLL is characterised by an increase in B lymphocytes in the blood, an increase in lymph nodes and spleen size in later stages, and a decline in blood levels in advanced stages, including anemia (low hemoglobin) and thrombocytopenia (low blood platelets).
CLL can be managed without chemotherapy
Dr. Gilad Itzhaki, director of the Hematology Institute at the Meir Medical Center in Kfar Saba, explains: “CLL is a chronic disease that generally progresses slowly. Therefore, most patients do not require treatment at the time of diagnosis but need to be monitored. It is crucial to remember that CLL patients have a higher risk of infections and other malignancies. Therefore, they should receive recommended vaccinations and undergo standard cancer screening tests, including skin mole checks,”. “CLL treatment is primarily required when patients show a significant enlargement of the lymph nodes and spleen and/or a significant decrease in other blood counts,” he adds. Advances over the past decade in understanding CLL’s mechanisms have led to targeted biological treatments that disrupt specific intracellular pathways. These treatments have been shown in multiple clinical trials to be safer and more effective than chemotherapy, and are now the standard treatment.
New treatments with reduced risk of cardiac side effects
Dr. Itzhaki notes that there are currently two main groups of biological drugs for CLL: BTK inhibitors and BCL2 inhibitors. “The first group includes several drugs that inhibit a protein called BTK, which is critical for transmitting signals in CLL cells, maintaining the cells’ vitality, and preventing their death,” he explains. “These drugs are taken orally and result in a rapid reduction in lymph node size. In the first few months, a significant increase in the number of white blood cells is expected, which is not dangerous and indicates the cells’ transition from the lymph nodes to the bloodstream. This phenomenon dissipates as the patient continues to take the drug. These treatments are given chronically, until disease progression or the need to cease due to side effects. Most patients take the drug without side effects or with mild and transient side effects, such as fever, rash, mild nausea, diarrhea, joint pain, headache, seasonal infections, and more. These effects usually do not necessitate dose reductions or discontinuation of treatment.”
However, several uncommon but important side effects to be aware of include atrial fibrillation, hypertension, and bleeding. Atrial fibrillation is a heart rhythm disorder that is not dangerous but typically requires medication, including anticoagulant treatment to prevent the formation of blood clots. Men, older adults with hypertension, and individuals with previous cardiac diseases are particularly at risk. Hypertension can develop over years of taking the drug and requires monitoring and sometimes dedicated treatment. Bleeding is usually superficial skin bleeding, but more severe bleeding is possible. It is recommended to stop treatment with these drugs around surgeries or other invasive procedures in consultation with the treating hematologist.
It’s important to note that we’re in a new era when it comes to new drugs in the BTK inhibitors group. In recent years, a second generation of drugs has been developed that are less toxic, with fewer cardiac side effects. This allows for the provision of effective treatments to patients that also have better safety profiles.
“The second group of drugs inhibits a protein called BCL2, which plays a significant role in preventing the death of CLL cells. These treatments are often given in combination with a monoclonal antibody against CD20 that is administered intravenously. The advantage of this treatment is that it results in a deep response, enabling the treatment to be stopped after a fixed period. For first-line patients, the treatment is given for one year, and for advanced-line patients, it is usually given for two years,” explains Dr. Itzhaki. The main side effects of this treatment are a decrease in the blood count, including a decrease in neutrophil-type white cells (neutropenia) and platelets (thrombocytopenia), a propensity to infections, and gastrointestinal side effects (diarrhea, constipation). Due to the risk of tumor lysis syndrome (TLS), the treatment is administered with a gradual dose increase under strict monitoring. Today, there is an option to combine BTK inhibitors with BCL2 inhibitors for a limited time, which is suitable for some patients based on their age and underlying diseases.
Choosing the most suitable treatment based on the patient’s characteristics
To select the most appropriate treatment for each patient, doctors typically examine multiple prognostic markers, including chromosome and mutation testing, which can aid in treatment selection. “In a minority of patients, there may be a deficiency in the short arm of chromosome 17 (deletion 17p) or a mutation in the TP53 gene, which are associated with a worse prognosis,” notes Dr. Itzhaki. Patients with significant cardiac morbidity may be better off avoiding BTK blockers, and patients with significant kidney damage may be better off avoiding BCL2 blockers.”
“Ultimately, the choice of the most appropriate treatment for each patient primarily depends on their overall health, underlying diseases, and preferences regarding treatment (ongoing vs. time-limited, pill-only treatment vs. treatment in conjunction with an antibody administered intravenously, etc.). It’s important to remember that there can be drug-drug interactions with other medications, so it’s recommended to consult the treating hematologist with any new medication the patient is taking,” Dr. Itzhaki adds.
So in conclusion, CLL is a disease that can be managed and lived with, reasonably?
“Absolutely. Chronic lymphocytic leukemia has seen a transformation in the last decade, becoming a disease that we manage to control and ensure quality of life and longevity for patients suffering from it. Through simple blood tests to count blood cells, and a high awareness of the issue, it is possible to diagnose and manage the disease correctly at an early stage. The treatment, when required, is without chemotherapy. The advanced biological drugs are safe and effective and they provide patients with a good quality of life alongside the disease and its treatment. This is wonderful news for patients. Moreover, the field continues to develop at a remarkable pace in terms of research. At the Meir Medical Center, we participate in several studies aimed at further improving the treatment of CLL patients.”
This article was produced in partnership with AstraZeneca.