Brief Overview of Types of Treatments
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Active or Disease-modifying Treatments
Treatments that aim to control, reduce, or even cure the CLL.
Targeted Therapy: Certain complex drugs that attack specific targets or pathways in cancer cells to avoid harming normal cells. Examples of targeted therapies are:
- BCL-2 Inhibitor: CLL cells are extremely dependent on BCL-2 to stay alive, much more so than normal cells. The BCL-2 inhibitor venetoclax blocks BCL-2 from preventing cell suicide. This can lead to very rapid “programmed cell death”. Venetoclax is one of the newest approved CLL drugs.
- CAR-T: Chimeric antigen receptor T cells therapy is an experimental cellular therapy that programs one’s immune system, specifically genetically modified T cells, a type of lymphocyte engineered to attack CLL Currently CAR-T is in clinical trials for CLL.
- Monoclonal antibody (mAb): A protein called an antibody is developed to attach to specific marker on CLL cells. This helps the immune system “see” the cancer cells so it can attack them. This medication does not affect most healthy cells but can deplete normal lymphocytes with similar markers to the CLL. There are many kinds of mAbs. The CLL commonly used approved monoclonal antibodies are rituximab and obinutuzumab, Others are being studied in clinical trials or are rarely used. These also may be called biological or immunotherapy.
- Signal Pathway Blockers: CLL cells strongly depend on signals received through the BCR (B-cell receptor) for many vital activities and ultimately their survival. Targeted therapies such as ibrutinib, idelalisib, duvelisib, zanubrutinib, and acalabrutinib can block this signaling at different steps along its pathway, often resulting in a profound effect on the cancer while sparing normal These “small molecule” medications can be taken orally.
- Tyrosine Kinase Inhibitors (TKI): These medications block the action of enzymes called tyrosine kinases (TK). TK play a critical role in cell signaling, growth, and division. Some TK are overexpressed in CLL and blocking them helps control CLL. Examples of these drugs include the signal blockers such as ibrutinib, idelalisib, duvelisib and several that are in development.
Chemotherapy (chemo): This is medicine that kills (cytotoxic) any rapidly dividing cell including cancer cells, but also normal cells in the hair and in the gut. This explains why hair loss and nausea often occur when receiving chemotherapy. CLL chemo includes alkylating agents (bendamustine, chlorambucil, and cyclophosphamide) and purine analogues (fludarabine). Both types damage the DNA of the target cells. In CLL, chemo is usually given with a mAb and the combination is called chemo-immunotherapy or CIT. There is little role for CIT in CLL with all the new agents.
Hematopoietic stem cell transplantation (HSCT) or “bone marrow transplant” involves the IV infusion of blood forming stem cells collected from bone marrow, peripheral blood, or umbilical cord blood. In CLL, this is almost always from a matched donor (allogeneic) in the hope that the new cells and newly imported immune system that comes with a successful HSCT will rid the patient of CLL. This cellular therapy is potentially curative, but is high risk.
Clinical Trials: By participating in a cancer clinical trial, patients with CLL / SLL have access to the newest and most advanced treatments, before they are widely available.
Supportive Care
This kind of treatment is used to relieve symptoms. It does not contribute to controlling or curing the disease but allows those other therapies to be better tolerated and may improve quality of life.
Anti-emetic: A drug used to prevent or reduce nausea and vomiting, a common side effect of some chemotherapy.
Complementary and alternative medicine: This includes medical approaches that are not currently part of standard practice. Complementary medicine is used along with standard medicine. Alternative medicine is used in place of standard medicine. Some examples include acupuncture, chiropractic, homeopathic, and herbal medicines. No complementary or alternative therapy has been proven to effectively treat CLL and all such therapies should be reviewed with your healthcare team.
Corticosteroids (steroids): These are similar to cortisol, a hormone that your body makes naturally and is a potent anti-inflammatory. For CLL, steroids are sometimes used to decrease some side effects of chemotherapy or to reduce strong reactions to monoclonal antibodies. Extremely high doses of steroids are sometimes used with a monoclonal antibody to treat CLL.
One of the many side effects of steroids is the increased risk of infection, already a problem in CLL. These medications include prednisone, prednisolone, methylprednisolone and dexamethasone.
Growth factors: These are substances made by the body to stimulate the bone marrow to produce blood cells. Some growth factors now can be man-made and used for treating low blood counts.
Red blood cell growth factors called erythropoietin-stimulating agents (ESA) and include Epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). White blood cell growth factors are called granulocyte colony stimulating factors (GCSF) and granulocyte macrophage colony stimulating factors (GMCSF). The newest compounds are smaller drugs that mimic platelet growth factors or thrombopoietin so that they can pharmacologically stimulate platelet production. These drugs are called TPO mimetics.
Immunoglobulins: These are proteins found in the liquid part of the blood (plasma). They work as antibodies and help to fight and prevent infections. Patients with CLL often have low levels of immunoglobulins, leading to recurrent infection. One type of immunoglobulin, IGG, may be replaced with a pooled blood product, IVIG (intravenous immunoglobulin) that may reduce the risk of infections and also treat certain autoimmune complications of CLL. It may also be given under the skin (sub-q).
Prophylaxis: Treatment to prevent a disease before it occurs. In CLL, antibiotics, anti-virals and anti-fungals can be used to prevent infections when patients are immunosuppressed.
Red blood cell transfusion: An intravenous infusion of packed red blood cells into the bloodstream to increase blood counts and help improve the symptoms of anemia, such as fatigue, shortness of breath and lightheadedness.
