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CLL is a form of cancer that is most diagnosed with in adults. Chronic Lymphocytic Leukemia is a type of white blood cell called a lymphocyte that doesn’t die when it normally would. Instead, it can accumulate in the blood, bone marrow and in the lymphatic system. Because of recent advancements in the field of CLL research and technology, there are many more options for treating CLL than in the past.
The ways in which CLL can be treated have evolved in recent years. The focus of treatment for CLL has shifted from only treating the symptoms of the disease and from aiming to give the longest period that the patient has without needing treatment, to a focus on survival and on reducing the adverse effects of treatment in order to improve the patient’s quality of life.
Understanding CLL and the Need for Personalized Care
No two patients with CLL are alike. The disease can progress more slowly in some patients than others, and at times may need to be treated before it becomes more aggressive. When deciding the best approach to treating a patient with CLL, the doctor will consider several factors, including a patient’s age, overall health, genetic markers, the stage of the disease and the degree to which it is symptomatically impacting the patient.
Improved diagnostic techniques have led to the identification of specific genetic abnormalities present in CLL. The knowledge of these abnormal genes has led to the development of targeted therapies that attack specific steps in the process by which CLL leukemic cells grow and survive. These new therapies have been evaluated in clinical studies and may offer different efficacy and safety profiles compared to chemotherapy used to treat this disease.
The Evolution of CLL Treatment
Chemotherapy has traditionally been used as the primary form of treatment for people suffering from CLL. Chemotherapy is associated with a range of side effects that can be significant for some patients and does not always provide long term relief from the disease.
Current strategies for the treatment of CLL have shifted from a general approach using chemotherapy to using therapies that specifically target the proteins and signaling pathways that are important for the survival and proliferation of CLL cells. These new treatments offer the potential for longer duration of control of the disease with fewer and less severe side effects than chemotherapy.
Today, in addition to traditional chemotherapy, there are several treatment options available for CLL. These include targeted therapies, monoclonal antibodies, combination therapies, and more recently, immunotherapy approaches.
Targeted Therapies: A Breakthrough
Targeted therapies represent an important development in CLL treatment (or small molecules). These are drugs which target a specific component in the leukemia cells to kill them. For example, BTK Inhibitors, which are a new class of targeted therapy that interferes with signaling to CLL cells and cause them to die. BTK Inhibitors have changed treatment approaches for many patients with CLL as they are usually very effective and given orally as tablets rather than by infusion.
BTK Inhibitors
BTK inhibitors block a signal which enables CLL cells to grow and to divide. The BTK inhibitors therefore can cause a slowdown of the disease and lead to a death of the cancer cells.
For this reason, BTK inhibitors have become the mainstay of treatment for many patients with CLL. These therapies are typically taken orally daily and have been proven to have demonstrated disease control and clinical benefit in certain patient populations.
BCL-2 Inhibitors
Another class of drugs that has recently been developed targets the BCL-2 family of proteins. In general, these proteins act to prevent apoptosis or programmed cell death. For cancer cells, including CLL cells, BCL-2 is often overexpressed and allows the cancer cells to survive indefinitely. Drugs that inhibit BCL-2, such as venetoclax, have shown demonstrated clinical activity in studies in patients with CLL and are often used as single agents or in combination with other therapies to induce deeper and more durable remissions.
The effects of BCL-2 inhibitors have been impressive, and they are increasingly used alone as well as in combination with other agents to deliver deeper and more sustained remissions.
The Role of Monoclonal Antibodies
Monoclonal Antibodies, such as rituximab, are proteins made in the lab that can recognize and attach to proteins on the surface of cancer cells. These proteins can then be used to tag the cancer cells so that the immune system can destroy them.
These therapies can be used alone or in combination with targeted agents for newly diagnosed patients as well as patients in relapse.
Immunotherapy and Emerging Innovations
Cancer Therapy Using the Immune System to Fight Leukemia and Lymphoma. This is a very exciting new area of cancer research. Instead of using chemotherapy or targeted cancer drugs to attack cancer cells directly, Immunotherapy or cancer therapy using the immune system can be used to fight cancer by making the body’s own immune system a more effective disease-fighting machine.
CAR T-Cell Therapy
CAR T-Cell Therapy for Leukemia and Lymphoma-Advanced Research in Progress for Relapsed or Refractory CLL: early clinical data are being evaluated for Patients with Aggressive or Difficult to Treat Leukemia.
Bispecific Antibodies
Other drugs are being tested to see if they can be used to treat patients with CLL and other cancers. One class of these emerging drugs is known as bispecific antibodies. These are made in the laboratory to bind to two different targets. For leukemia drugs being tested as cancer treatments, one target is the cancer cell and the other is a part of the immune system. When a bispecific antibody binds to a leukemia cell and a part of the immune system, it can direct the immune system to attack the cancer cell.
These new approaches to cancer treatment may provide more options for future cancer patients.
The Importance of Genetic Testing
By defining a patient’s genetic or molecular characteristics, and how their leukemia may behave, or how a patient may respond to therapy, testing can help determine what type of treatment may be best for a patient.
In CLL patients who have certain genetic abnormalities such as a TP53 mutation or a 17p deletion, the disease behaves in a more aggressive manner and may require treatment with specific therapies and possibly more frequently than patients without these abnormalities. Furthermore, in some cases, certain therapies may not provide as much benefit for a particular patient with CLL as they do for another patient. For example, studies have shown that some patients with CLL who have a 17p deletion do not benefit from therapies that target the CD20 protein on the surface of the cancer cells and therefore these therapies should likely be avoided in these patients. As a result, genetic and molecular testing may be considered as part of clinical evaluation by healthcare professionals to determine if they have any genetic abnormalities that could play a role in determining the type of treatment that is best for them.
This is the backbone of the current CLL management today.
Improving Quality of Life During Treatment
It is increasingly important to us that in addition to extending the survival of patients with CLL we also attempt to improve their quality of life. The newly developed therapies are designed to be as gentle as possible, whilst at the same time maintaining effective disease control.
Patients today often experience:
- Reduced need for hospitalization
- More convenient oral medications
- Fewer severe side effects
- Periods of remission in some patients
- Greater ability to maintain daily activities
Supportive care, for example, in the form of prevention of infections, in symptom control and by regular check-ups, play a very important role.
Looking Ahead
The future of CLL will be shaped by ongoing clinical trials, where new drug combinations are being tested, next generation targeted treatments are being developed, and new forms of immunotherapies are being explored. It is hoped that future CLL treatments will allow for deeper remissions, reduced treatment duration and the ability to treat patients with relapsed CLL.
The CLL treatment should be focused on achieving deeper remissions in more patients for longer periods of time. In addition, researchers are working to reduce the length of time that a patient is required to be in treatment for. New therapies are also being developed to treat relapsed or refractory CLL as well as to overcome the disease’s resistance to current cll treatment options. With continued research and advances in CLL treatment, there are many new and innovative options available to the patient and their physician to create the appropriate CLL treatment plan based on individual clinical factors.
Looking Forward
CLL today has transformed into a disease to be treated over the last decade with targeted therapies, with multiple monoclonal antibodies, and most importantly with immunotherapies that have greatly impacted the treatment for CLL. The genetic tools to help select the best CLL treatment have also greatly evolved, providing new avenues for hope for each CLL patient.
