Two types of targeted therapies are used against non-Hodgkin’s lymphoma. Newer treatments use small-molecule drugs to target a gene or protein responsible for allowing cancer to grow. Monoclonal antibodies, which have been used for more than a decade, seek out and damage cancer cells or prompt the immune system to attack particular cells. Also called immunotherapy, this treatment relies on immune-system proteins that are produced in the laboratory from a single source.
Clinical Studies of Small-Molecule Drugs
The identification of signaling pathways involved in cancer has led to new drugs that target the specific molecules that help start and promote cancer growth.
New targeted therapies for non-Hodgkin’s lymphoma being studied in clinical trials at Seattle Cancer Care Alliance (SCCA) include idelalisib, which is an oral PI3K delta inhibitor, and ABT-199, a potent and selective Bcl-2 inhibitor.
Drugs known as PI3K inhibitors block signals from the PI3K pathway, which regulates key cell functions, such as growth and division. This pathway is overactive in some cancers, including slow-growing non-Hodgkin’s lymphoma and chronic lymphocytic leukemia (CLL). Blocking signals from the pathway can slow down or eliminate the out-of-control growth of mutated cells.
ABT-199 is designed to selectively block the function of Bcl-2 proteins in order to promote cell death (apoptosis). Bcl-2 proteins play a central role in regulating cell death activity. Non-Hodgkin’s lymphoma, CLL, and other B-cell cancers are marked by high levels of Bcl-2 proteins.
For B-cell lymphoma, doctors often use an antibody called rituximab (Rituxan), in addition to chemotherapy regimens. Rituximab targets a specific molecule on lymphocytes (white blood cells) and triggers other immune system proteins to kill them. Unlike most targeted therapy using antibodies, rituximab does not differentiate between cancerous and normal lymphocytes. Our bodies can function without lymphocytes, however, and over time the body forms new ones.
Antibodies like rituximab can be tagged with a radioactive atom and used to deliver a one-two punch: The antibody concentrates radiation on lymphocytes plus triggers an immune system attack against the targeted cells.
Getting Targeted Therapy for Non-Hodgkin’s Lymphoma
Rituximab is standard care for many lymphomas and can be given at any of the SCCA infusion centers.
SCCA patients who meet the criteria may choose to take part in clinical studies of small-molecule targeted therapies such as PI3K and ABT-199. See information about lymphoma clinical studies that are open and accepting patients through SCCA.
Targeted therapy—both antibody and small-molecule drug—is usually given in cycles, which means you receive an infusion of your drugs through an intravenous line (by IV) on one day, and then you wait a few weeks before receiving your next dose. This gives the drugs time to have an effect and also gives your body some time to recover before getting more. You may want to bring a friend or family member to sit with you during treatment, which sometimes takes several hours.
The schedule depends mainly on your type of lymphoma. For indolent forms of non-Hodgkin’s lymphoma, targeted therapy is given indefinitely to keep the disease under control. With faster growing cancers, targeted therapy, along with chemotherapy, is given for four to six months with the aim of curing the disease.
Targeted drugs work differently than standard chemotherapy drugs, which affect both cancer and fast-growing normal cells. For this reason, targeted therapies often have different side effects, which may be less severe. Although rituximab targets all lymphocytes—both cancerous and normal—our bodies can function without them, and over time the body forms new lymphocytes.
The side effects of targeted therapies vary greatly from person to person and depend on the type and dose of drugs given, how they are given, and the length of time they are given. Your treatment team can tell you about the side effects that are most common with your treatment. Let your team know about any side effects you experience.
For general information to help you cope with side effects, visit our section on symptom management.