Lymphoma is a cancer that develops in the lymph system, a network of vessels and nodes that forms part of the body’s immune system.

Lymphomas are grouped into two categories: Hodgkin and non-Hodgkin, the latter being by far the more common form. But even that disease is not one but many, with subtypes based on the kind of cell it affects. In addition, the disease can be classified as indolent (slow-growing) or aggressive, and low-, intermediate-, or high-grade.

New drugs, new direction
Many new drugs are currently being evaluated for lymphoma treatment, and most are much different from traditional chemotherapy. This trend began with the introduction of rituximab, a biologic agent (in this case, an antibody) that specifically targets the immune cells from which most lymphomas arise. When added to traditional chemotherapy, rituximab has increased the cure rate in people with aggressive B cell lymphomas.

For low-grade lymphomas, researchers predict that future regimens will contain less chemotherapy and more long-term use of targeted agents. New drugs being developed with an eye toward chronic therapy include antibodies (with different targets than rituximab’s), therapeutic vaccines, and other targeted oral therapies.

“Previously, we treated low-grade lymphomas like aggressive lymphomas, using aggressive chemotherapy,” says Ajay K. Gopal, MD, associate member at the Fred Hutchinson Cancer Research Center in Seattle, who has been testing a vitamin A derivative in conjunction with rituximab. “But maybe we should treat low-grade lymphomas more like hypertension—aiming at maintenance rather than cure. If pills and an occasional infusion keep the lymphoma from progressing, we’d consider it a success because it avoids the toxicity of chemotherapy.”

Intensifying treatment
For potentially curable lymphomas, targeted therapy may also provide ways to intensify—and improve—treatment. At Fred Hutchinson, high-dose radioimmunotherapy is being used for lymphomas that have relapsed after initial treatment. “By targeting the tumor with radiation therapy, we can spare healthy tissues and reduce toxicity,” says Dr. Gopal.

In radioimmunotherapy, a radiation source is attached to lymphoma-
targeted antibodies, which are injected into the body. The radiation dose can be manipulated by changing the amount of antibody injected. High-dose radioimmunotherapy is combined with a stem cell transplant. Since high radiation doses can injure stem cells, the patient’s stem cells are removed before radiotherapy is given. They’re returned about two weeks later, after the radiation has been cleared from the body, to restore a working immune system.

Dr. Gopal says this approach may improve survival rates in people with relapsed lymphoma, compared with total-body radiation plus chemotherapy or chemotherapy alone followed by transplantation.