Sylvester Comprehensive Cancer Center

Radioimmunotherapy Now Available As Outpatient Treatment for Lymphoma at UM/Sylvester

09.15.2004

Two new dual-action radioimmunotherapy agents, Bexxar and Zevalin, are now available as outpatient therapies to some patients with low-grade or transformed non-Hodgkin’s lymphoma at the University of Miami Sylvester Comprehensive Cancer Center. Each drug is a unique dual-action therapy that combines a radioactive isotope and an immunological antibody into one treatment, using both radiation therapy and the patient’s own immune system to fight cancer.

“We now have two great agents which are easy to use and are well tolerated by the patients,” said Aldo N. Serafini, M.D., professor of radiology and medicine in the Division of Nuclear Medicine at the UM School of Medicine. Now that UM/Sylvester has received state licenses to administer both Bexxar and Zevalin as outpatient treatments, the therapies are covered by Medicare and private health insurers.

“Radioimmunotherapy is a very, very valuable tool to have in the inventory,” said Izidore Lossos, M.D., associate professor of clinical medicine in the Division of Hematology Oncology at UM/Sylvester. “Patients with follicular lymphoma have a history of repeated relapse and each relapse is more resistant to chemotherapy. But this disease is very sensitive to radiotherapy like the isotopes in these agents.”

UM/Sylvester and Jackson Memorial Hospital are now the only centers in South Florida offering two choices for outpatient radioimmunotherapy. Both Bexxar and Zevalin have been shown to be effective in lymphomas that don’t respond well to chemotherapy and bone marrow transplantation. “Lymphoma is so variable, there are so many subtypes of lymphomas, that having an academic center available with new treatments like this is critical to patients,” said Lossos.

This year in the United States approximately 54,370 people will be diagnosed with non-Hodgkin’s lymphoma, which affects the blood, bone marrow and lymphatic tissues. Approximately 23,400 will die from the disease. It accounts for about 4% of both cancer cases and cancer deaths in the U.S. In Florida alone more than 2,600 new cases will be diagnosed and more than 1,100 people will die. Non-Hodgkin’s lymphoma is the most common type of lymphoma in both men and women nationwide, with about 300,000 Americans currently afflicted. Between 25 and 40 percent have follicular NHL. To learn more about this therapy, please call (305) 243-1000.

In a multi-center, single-arm clinical trial in patients who had received an average of four prior chemotherapies and who had Rituximab-refractory disease, 63 percent (22 of 35) responded to Bexxar. The median duration of response was 25 months. The results of this study were supported by demonstration of durable objective responses in four single-arm studies enrolling 190 patients evaluable for efficacy with Rituximab-naïve, follicular non-Hodgkin’s lymphoma with or without transformation, who had relapsed following or were refractory to chemotherapy. Determination of clinical benefit of the Bexxar therapeutic regimen was based on evidence of durable responses without evidence of an effect on survival.

A single-arm study of Zevalin was conducted in 30 heavily-treated patients with relapsed or refractory, low grade or follicular NHL or transformed B-cell NHL. Twenty patients, or 67-percent, showed some response to Zevalin, with response durations ranging from four to 17 months. Earlier trials showed remissions that were two months longer, on average, than treatment with the monoclonal antibody Rituximab alone.

The immunological agent in Bexxar is Tositumomab, a monoclonal antibody designed to target this type of lymphoma and destroy it. The radiological agent is Iodine-131, a beta-isotope which is delivered right to tumor cells by the antibody. The Bexxar therapeutic regimen is given as a single, short course of treatment in four visits over a period of one to two weeks and is specifically dosed based on an individual’s drug clearance rates. “We take a small amount of the antibody, inject it into the patient and make sure it distributes and behaves as we expect it to,” said Serafini.

This test dose allows physicians to tailor the dose exactly to the patient’s ability to process the drug so they don’t receive too little to fight the disease or too much for their body to handle. “They receive the antibody first which essentially clears a path to the tumor in the lymph nodes and elsewhere by clearing the circulating lymphocytes in the blood,” said Serafini. “Then they receive a dose of the antibody conjugated together with the radioactive material which targets the tumor.”

By combining a monoclonal antibody that preferentially binds to CD20-positive B cells with radioactive iodine, Bexxar delivers the radiation dose to target B cells inside the body. The Iodine-131 radioisotope in Bexxar emits both gamma rays that allow the treatment team to measure the amount of radiation in a patient’s body, and beta particles, which contribute to the therapeutic effect.

To be extra careful, because this treatment does involve exposure to radiation, patients are administered potassium iodide to protect their thyroid glands, and are encouraged to take some precautions for two or three days after the treatment. Just like health care providers take care to avoid overexposure to X-rays, patients are told to limit intimate contact, and to avoid close proximity to young children. These steps are taken as an extra measure of safety. “We don’t discharge patients until they’re safe to be discharged,” said Serafini.

In the dosimetric step, involving three visits to the treatment center, the nuclear medicine physician or radiation oncologist determines the amount of radiation that will be given in the therapeutic step and whether the distribution of the antibody in Bexxar is normal. The therapeutic step is completed on the fourth and final visit, the treatment day, during which the specific dose of radiation is administered.

Zevalin combines the Ibritumomab monoclonal antibody with one of two radioactive isotopes; Indium-111 or Yttrium-90. The Zevalin therapeutic regimen is administered in two steps: Step one includes one infusion of Rituximab preceding In-111 Zevalin. Step two follows step one by seven to nine days and consists of a second infusion of Rituximab followed by Y-90 Zevalin. The Zevalin dose is based on body weight and other factors.

A team of medical professionals, including hematologist oncologists, radiation oncologists, nuclear medicine physicians, nurses, hospital pharmacists, radiopharmacists, radiation safety officers, and nuclear medicine technologists, work together to deliver these regimens.

UM/Sylvester was founded in 1992 to provide comprehensive cancer services and today serves as the hub for cancer-related research, diagnosis, and treatment at the University of Miami School of Medicine. UM/Sylvester handles more than 1,100 inpatient admissions annually, performs 2,800 surgical procedures, and treats 2,900 new cancer patients. All UM/Sylvester physicians are on the faculty of the University of Miami School of Medicine, South Florida’s only academic medical center. In addition, UM/Sylvester physicians and scientists are engaged in more than 150 clinical trials and receive more than $30 million annually in research grants.

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