The University Record, June 25, 1996

Therapy shows promise in fight against non-Hodgkins lymphoma

An innovative treatment using radioactive antibodies that target and destroy cancer cells appears to shrink tumors in patients who have failed numerous conventional therapies for the most common form of non-Hodgkin's lymphoma.

Comprehensive Cancer Center researchers presented findings from a Phase I/II study of radioimmunotherapy in patients with B-cell lymphoma at the American Society of Clinical Oncology annual meeting in May.

The therapy, which involves injecting into the blood stream monoclonal antibodies armed with radioactive iodine to zero in on cancer cells and destroy them, caused tumors to greatly shrink or completely disappear in nearly three-fourths of the 47 patients treated, with minimal or no side effects in many of the treated patients.

"Results are particularly promising in patients with recurrent low-grade lymphoma---a slow-growing but relentlessly progressive and incurable form of the disease that accounts for nearly 40 percent of newly diagnosed B-cell lymphoma cases," says Mark S. Kaminski, associate professor of internal medicine and principal investigator for the study funded by the National Institutes of Health. Two-thirds of the low-grade lymphoma patients had complete remissions (no evidence of cancer), and 19 of 21 responded to the treatment.

The monoclonal antibody used in this study, known as anti-B1 and produced by Coulter Pharmaceutical of Palo Alto, Calif., is engineered to attach to a protein found only on the surface of B-cells, a type of white blood cell that produces disease-fighting antibodies. The targeted tumor cells receive a greater accumulation of lethal radiation while normal tissue is spared. Once bound to the cell, the antibodies also stimulate the immune system to kill any remaining cancer.

Nearly half of the patients studied experienced complete remissions longer than any previously induced by chemotherapy---regardless of the type of lymphoma or the extent of the disease---with the average patient remaining cancer-free for at least 16 months. Several patients have had no return of their cancer for nearly three years. "These results are particularly striking given that the majority of patients had disease that was unresponsive to the chemotherapy, including bone marrow transplants," says Kaminski, who also directs the Cancer Center's Lymphoma/Leukemia Program.

In the Phase I/II study, Kaminski and co-investigator Richard L. Wahl, professor of internal medicine and of radiology, were able to determine the optimal dose of radiation by first injecting the antibody with only a small amount of radioactive iodine attached. This test dose allowed researchers to use individualized information to develop an appropriate therapeutic dose for each patient.

According to Kaminski, the treatment consists of two one-hour injections given about one week apart---first a test dose and then a therapeutic dose. The second injection requires patients to spend a weekend in the hospital. "The treatment is short, simple and extremely boring, which is a delight for the patients," he says. Kaminski also says anti-B1 therapy appears to be cost-effective, reducing hospital stays and days lost from work, compared to conventional chemotherapy that requires multiple treatments over the course of several months.

Non-Hodgkin's lymphoma, a form of cancer that affects the blood and lymph tissues, typically strikes in early middle age and often resists standard therapies. It is estimated that nearly 53,000 Americans will be diagnosed this year with non-Hodgkin's lymphoma and nearly half will die of the disease. More than 80 percent of these cases involve malignant B-cells.

Multi-center trials currently are under way to confirm the U-M findings, and researchers are working with the Food and Drug Administration to help bring the therapy to market. Within the year, Kaminski and Wahl also plan to begin studying radioimmunotherapy in patients with low-grade lymphoma who previously have not been treated with chemotherapy. "Given our current results, we can only think the therapy will be even more effective when it's given as the first treatment, before a patient is exposed to toxic effects of therapies," says Kaminski.

For more information about radioimmunotherapy using the B1 antibody, call the Medical Center at (800) 742-2300, ext. 6210.