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Adapted from the NCI Cancer Bulletin, vol. 5/no. 21, Oct. 21, 2008 (see the current issue ³).

Treatment with a radiolabeled monoclonal antibody appears to be highly effective as consolidation after first-line therapy in patients with indolent, advanced-stage follicular lymphoma, according to results of a large phase III clinical trial published October 14, 2008, in the Journal of Clinical Oncology (see the journal abstract ⁴).

The results showed that consolidation therapy - a form of adjuvant therapy after initial or "induction" therapy to induce remission - with a single dose of yttrium-90 (⁹⁰Y)-ibritumomab tiuxetan (Zevalin®) significantly improved progression-free survival in all patient subgroups compared to patients in the control arm, who received induction therapy but not consolidation therapy. ⁹⁰Y-ibritumomab is a monoclonal antibody with a radioactive isotope attached to it.

The improvement in progression-free survival held up regardless of whether patients had a complete response (CR) or partial response (PR) to induction therapy: 53.9 months vs. 29.5 months for CR and 29.3 months vs. 6.2 months for PR. In addition, the multinational research team, led by investigators at the Universitair Medisch Centrum Utrecht in the Netherlands, reported 77 percent of patients in the treatment arm with a PR to induction therapy "converted" to a CR after receiving ⁹⁰Y-ibritumomab.

"This constitutes one of the highest PR-to-CR conversion rates reported in published phase III randomized studies in first-line follicular lymphoma," they wrote. Considering the efficacy and modest toxicity associated with ⁹⁰Y-ibritumomab in the trial, consolidation therapy with this monoclonal antibody "may be considered as part of the current treatment algorithm of follicular lymphoma," they concluded.

Seattle-based Cell Therapeutics, Inc., which manufactures ⁹⁰Y-ibritumomab, is now seeking approval from the U.S. Food and Drug Administration to begin marketing the drug for first-line consolidation therapy in patients with follicular lymphoma, a type of non-Hodgkin lymphoma. ⁹⁰Y-ibritumomab is already approved in the United States to treat follicular lymphoma that has recurred or is unresponsive to available treatment regimens.

The Firstline Indolent Trial included 414 patients from 77 medical centers across Europe. Patients received a variety of induction therapy regimens, which included different chemotherapy agents and, in approximately 15 percent of patients, also included the monoclonal antibody rituximab ⁵ (Rituxan®). After induction therapy, patients were randomized to no consolidation therapy or consolidation with a two-course "priming" dose of rituximab followed by a single dose of ⁹⁰Y-ibritumomab. Because of the limited follow-up, there are no data from the trial yet on overall survival.

Given the positive results seen even in patients who received less aggressive induction regimens, the authors added, ⁹⁰Y-ibritumomab "has the potential to maximize tumor response without using aggressive induction regimens and may reduce the need for aggressive chemotherapy."

The limited use of rituximab as part of induction therapy in the trial hinders the interpretation of its results, Dr. Oliver W. Press, chair for lymphoma research at Fred Hutchinson Cancer Research Center, cautioned in an accompanying editorial ⁶. While calling the trial a "landmark study," he noted that, based on results from several phase III clinical trials, combining rituximab "with each cycle of induction chemotherapy has become a worldwide standard."

Even so, says Dr. John Leonard, director of the Center for Lymphoma and Myeloma at Weill Cornell Medical College in New York, its good safety profile and the fact that it is well tolerated by patients makes ⁹⁰Y-ibritumomab "particularly attractive for [use in] older patients," who may not handle more toxic chemotherapy regimens very well.

Radioimmunotherapy, as the use of radiolabeled monoclonal antibodies is often called, has not been widely adopted, Dr. Leonard notes, in part because it's not as easy for oncologists to use as other available treatments, including rituximab. For one thing, it has to be administered in a facility specially equipped to handle radioactive compounds.

A number of trials, Dr. Leonard continues, are ongoing that should help to clarify the role of radioimmunotherapy in patients with newly diagnosed, advanced follicular lymphoma.

Glossary Terms

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

Treatment that is given after cancer has disappeared following the initial therapy. Consolidation therapy is used to kill any cancer cells that may be left in the body. It may include radiation therapy, a stem cell transplant, or treatment with drugs that kill cancer cells. Also called intensification therapy and postremission therapy.

Effectiveness. In medicine, the ability of an intervention (for example, a drug or surgery) to produce the desired beneficial effect.

Initial treatment used to reduce a cancer. First-line therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called induction therapy, primary therapy, and primary treatment.

A type of cancer that grows slowly.

Initial treatment used to reduce a cancer. Induction therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called first-line therapy, primary therapy, and primary treatment.

A type of protein made in the laboratory that can locate and bind to substances in the body, including tumor cells. There are many kinds of monoclonal antibodies. Each monoclonal antibody is made to find one substance. Monoclonal antibodies are being used to treat some types of cancer and are being studied in the treatment of other types. They can be used alone or to carry drugs, toxins, or radioactive materials directly to a tumor.

A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

The length of time during and after treatment in which a patient is living with a disease that does not get worse. Progression-free survival may be used in a clinical study or trial to help find out how well a new treatment works. Also called PFS.

Any compound that has been joined with a radioactive substance.