Leukemia is more frequently observed in older individuals. Chronic Lymphocytic Leukemia (CLL) is among the most commonly diagnosed types in this age group. It is characterized by an increased number of B lymphocytes, a type of white blood cell. Over time, some of these B cells can become cancerous. Typically, CLL develops very slowly and, in some cases, may not require treatment for many years. The disease is diagnosed in people of all ages. However, most are diagnosed when they are 60 or older. Although the disease is considered to be incurable at present, it is not always fatal and many people live for long periods of time after they have been diagnosed with the condition. Some people experience few or no symptoms for many years before requiring treatment.
There has been a notable change in the management of CLL with the advent of targeted therapy for CLL over the last decade. Unlike traditional chemotherapy that kills off all fast growing cells in the body, targeted therapy targets the specific molecular pathways that the CLL cells use to keep themselves alive. This approach has been associated with disease control and a different side effect profile compared to traditional chemotherapy in clinical settings. Furthermore there have been multiple drugs developed that target specific pathways that are involved in the growth and survival of CLL cells, thus expanding available treatment options for patients.
New and innovative ways of treating CLL using targeted therapy are rapidly being introduced. While they have many benefits to both patients and providers, there are also many implications for health systems that need to be explored.
Understanding the Shift Toward Targeted Therapy
Many of the current therapies used to treat CLL were designed to mimic aspects of the body’s natural immune response and were developed to treat a variety of different cancers. As a result, much of the initial research on CLL therapies was focused on how to use conventional chemotherapy in combination with monoclonal antibodies to treat patients with this disease. Although these therapies have proven to be effective for some patients with CLL, they often have significant side effects that can make patients very sick. In addition, while some patients with higher risk forms of CLL may benefit from these therapies, many patients will not. Thus, in recent years there has been an increased focus on the development of targeted therapy for CLL. These therapies, which are based on an understanding of the biology of the leukemia, are designed to specifically target the cells that cause the disease.
The molecular basis for CLL helps to explain how targeted therapy for CLL works. Research into the molecular causes of CLL has identified several key proteins that are involved in the growth and survival of CLL cells. Some of these proteins are also involved in the resistance of CLL cells to natural cell death. By targeting these proteins, it is possible to develop targeted therapies for CLL that interfere with the key pathways involved in the disease. These therapies offer an alternative to traditional chemotherapy that is more specific and potentially less toxic.
The different ways in which targeted therapy for CLL can be used represent a major shift from how chemotherapy for CLL has been used in the past. Rather than relying on the same chemotherapy regimens for all patients with similar disease features, targeted therapies can be used in a more individualized fashion for each patient. These agents can be chosen on the basis of a number of different factors including the patient’s overall clinical and disease characteristics, specific genetic features of the leukemia, and the patient’s risk group.
How Targeted Therapy Works
The primary aim of Targeted Therapy for CLL is to interfere with the leukemia cells’ internal processes enabling them to grow, to survive, to spread and to be resistant to their treatment. Thus, such treatments attack leukemia cells by targeting their unique biology rather than targeting all rapidly dividing cells in the body and therefore in contrast to the effects of chemotherapy, they do not affect other body cells that are rapidly dividing, for example, cells in hair roots, in the gut, etc.
Other treatments stop the signals for growth of the CLL cells and still others can cause the CLL cells to undergo programmed cell death (apoptosis) thus eliminating them from the body of the patient.
Common treatment targets include:
- Bruton’s Tyrosine Kinase (BTK)
- BCL-2 protein
- Surface proteins found on CLL cells
- B-cell receptor signaling pathways
Even though these treatments are more specific, they have different side effects. Thus, patients have to be monitored throughout the treatment. However, most of them are able to maintain an effective disease control with only a few side effects.
Benefits for Patients
Leukemia treatments have seen significant changes with the advent of targeted cancer targeted therapy for CLL. Several cancer targeted therapies have been found to provide long-lasting disease control in many patients with various types of CLL, including those with high-risk features such as 17p deletions.
Since targeted CLL medications are mostly taken orally, as opposed to IV chemotherapy, patients have the opportunity to continue many of their normal activities. Patients are able to work, socialize, and otherwise continue life as usual. For many patients, targeted CLL medications provide a very good quality of life during treatment for CLL.
Some of the key patient benefits include:
- Longer progression-free survival in many patients
- Reduced reliance on chemotherapy
- Convenient oral treatment options
- Improved quality of life for many individuals
- Effective treatment for certain high-risk disease subtypes
- More personalized treatment planning
Every person is different and as such, will experience different outcomes as a result of targeted therapy for CLL. There are a number of factors that will determine how a person will react to any form of treatment including their age, overall health, the presence of any genetic mutations and previous treatment(s).
Challenges and Considerations
While targeted therapies do have many advantages for the patient with leukemia, there are also some challenges to the use of these medications. Many of these medications must be taken on a continuous basis for long periods of time. Patients must remember to take the medication on time in order to gain the full benefit of the treatment. If the patient is to obtain the best results from the therapy, it is crucial that the patient is able to take the medication on a regular basis for long periods of time.
Most importantly side effects which require medical attention will differ from those typically encountered with chemotherapy and have to be treated in an appropriate manner by the patient’s health care team.
Potential considerations include:
- Increased risk of infections
- Bleeding complications with certain medications
- Heart rhythm abnormalities in some patients
- Drug interactions with other prescriptions
- Regular blood tests and clinical monitoring
- Financial considerations related to long-term therapy
It is important to discuss with healthcare providers about any concerns or fears about side effects or potential interactions of CLL medications with other prescribed medications.
Implications for Healthcare Providers
In the era of targeted therapies for CLL, managing patients has become more complex. The choice of a first line treatment for a patient with CLL increasingly depends on the results of the molecular tests, as well as other characteristics of the patient’s disease. As a result, oncologists must navigate an expanding body of clinical information to support informed and effective patient management decisions.
Modern CLL management begins with molecular testing to understand the individual’s CLL at the molecular level in order to select the best targeted therapy. The testing helps to identify particular abnormalities in the cancer cells which can guide treatment decisions with the aim of achieving the best results with minimal side effects.
Clinicians are able to monitor their CLL patients on treatment by regular reviews and blood tests. These appointments also allow clinicians to assess their patients’ treatment and manage any side effects that have occurred. Clinicians also are able to alter or change their patients’ treatment if needed, and provide their patients with information and resources that can aid them in adhering to their long-term treatment plan.
The new CLL treatments have the potential to change the way patients and their healthcare providers can make decisions about treatment. This approach to cancer care will require patients and their healthcare providers to make joint decisions about the best treatment options.
Impact on Health Systems
Many innovative drugs have been developed for the treatment of CLL, resulting in many improved outcomes for patients. New therapies, however, require a change in how health care is delivered and how resources are allocated and managed within health care systems.
Health systems must make investments in precision diagnostics to enable individualized treatment approaches with targeted agents. Many health systems are increasing the use of molecular tests to guide initial treatment as well as subsequent management of relapsed or refractory CLL.
As well as requiring an increase in the use of molecular diagnostics for precise treatment, healthcare organizations are slowly undergoing a transition in terms of where the administration of chemotherapy is to take place. Chemotherapy can be given on an in-patient basis or on an out-patient basis and for the majority of targeted therapy treatments, this can be an oral medication given at home by the patient, thereby reducing the need for in-patient visits for chemotherapy administration. Many of these treatments are given on an out-patient basis which means that patients are not required to stay in a hospital for treatment, reducing the number of stays in hospital that a patient would have. This can make treatment more convenient for patients. In addition to this, a greater focus on ensuring that patients are taking the correct amount of their medication, all of the time, will be necessary to achieve the best results from these treatments.
Key health system considerations include:
- Greater demand for molecular diagnostic testing
- Expanded outpatient oncology services
- Increased focus on medication adherence programs
- Collaboration among multidisciplinary care teams
- Long-term budgeting for innovative therapies
Striking a balance between access to the best cancer treatments and the financial strain they place on a world’s health care systems is an ongoing challenge.
Future Directions in CLL Treatment
In addition to the current treatments under investigation, new targeted agents as well as new treatment strategies (used either alone or in combination) for the management of patients with CLL are currently under investigation with the goal of providing improved clinical outcomes and/or reducing the occurrence and severity of long-term side effects.
Research into new treatments for CLL is currently underway. The majority of new agents are targeted and are being tested in monotherapy as well as in combination with other agents. Studies are also being designed to look at the role of treatment in certain subgroups of patients with CLL, and to test new approaches to the treatment of refractory CLL. Some of the current research goals are to develop fixed-duration treatments, to improve the management of relapsed or refractory CLL, and to identify biomarkers that can be used to predict a patient’s individual response to a particular treatment. These future advances in precision medicine are likely to result in even more individualized treatment for patients with CLL in the years to come.
Other future strategies will include the use of a combination of targeted agents, and targeted agents with immunotherapies, and other novel approaches to treat patients with CLL to induce deeper and more durable complete remissions in patients with this disease, whether they are newly diagnosed or have relapsed or refractory disease.
Conclusion
Targeted therapies have revolutionized the management of patients with CLL and are now considered the cornerstone of treatment for this disease. In fact, targeted agents have been associated with improved clinical outcomes in certain patient populations with CLL when compared to traditional chemotherapy, leading to a more prolonged period of disease control and improved quality of life for patients.
Targeted treatments of CLL are enabling cancer patients to be treated for longer periods of time and leading to a better quality of life. For healthcare professionals the new class of treatments require an understanding of how to utilize molecular diagnostics to determine the best individualized treatment. Patients with this disease need to be monitored on an ongoing basis and healthcare systems will need to incorporate new approaches to deliver precise cancer care on an outpatient basis. In addition, a number of aspects must be taken into account by health systems in terms of organization and funding of cancer care.
However, targeted therapies for CLL will continue to be at the center of clinical research, hopefully to be used as part of innovative and effective treatment strategies for leukemia patients. In summary, a continuous innovation of targeted cancer therapies in conjunction with a personalized treatment approach of a patient with leukemia will in the long run improve therapeutic results and be the cornerstone of cancer treatment in the future.
