ROCHESTER, Minnesota—Ibritumomab tiuxetan (Zevalin) significantly improves quality of life for patients with low-grade, follicular, or transformed non-Hodgkin’s lymphoma (NHL) patients, according to the results of a phase-III study reported by Gregory A. Wiseman, MD. "Low-grade lymphoma is not a curable disease, but patients live for a long time with it," said Dr. Wiseman, lead researcher and assistant professor, Radiology Department, at the Mayo Clinic in Rochester, Minnesota. "We want to know how patients are feeling, especially if they’re going through difficult treatments. What we discovered is that after receiving Zevalin, patients’ quality of life was good."
The monoclonal antibody rituximab(Drug information on rituximab) (Rituxan) has been approved by the Food and Drug Administration (FDA) for several years. Trials with Zevalin, a murine anti-CD20 monoclonal antibody combined with the radioactive isotope yttrium 90, are ongoing in preparation for FDA submission. Studies have found that using Zevalin after administering rituximab improves the ability of the monoclonal antibody to reach and destroy cancer cells, Dr. Wiseman said.
In the current phase-III study, patients with relapsed or refractory low-grade, follicular, or transformed NHL were randomized to the Zevalin radioimmunotherapy arm or the rituximab immunotherapy arm. Among the study aims was the evaluation of tumor response, functional ability, and social, psychological, and emotional factors to determine if adding Zevalin to rituximab improved the patients’ quality of life. Patients in the Zevalin arm received two doses of 250 mg/m2 rituximab, then 0.4 mCi/kg of Zevalin. The control group received 4 weekly doses of 375 mg/m2 rituximab only.
Study Results
Median patient age was 59 years; 51% were female; and 90% had stage III or IV lymphoma. Thirty-nine percent had cancer that involved the bone marrow. The patients in the Zevalin group had an 80% overall response rate to their treatment, while those in the rituximab control group had a 56% overall response rate. These figures include complete and partial responses (tumor shrinkage of at least 50%).
Quality-of-life issues were subjectively evaluated by patients using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The FACT-G questionnaire administered to patients elicited information about their physical state, social and family relationships, their relationships with their physicians, and their emotional and functional well being. In the Zevalin group, patients completed the FACT-G at baseline, 1 day after infusion and at 1, 2, 3, 6, 9, and 12 months afterward. The rituximab group took the survey at baseline, immediately after their last infusion, and at 1, 2, 3, 6, 9, and 12 months afterward.
Sixty-two percent of patients in the Zevalin group completed the baseline and 3-month FACT-G surveys. Fifty-one percent of patients in the rituximab group completed the questionnaires. When looked at overall, the scores for Zevalin improved significantly at 3 months, while the scores for the rituximab group were not statistically different at 3 months. Emotional quality of life improved significantly for patients in both treatment groups, but physical and functional well being improved significantly only with Zevalin.
As indications of their physical well being, patients reported that they had more energy, spent less time in bed, and had less pain than before treatment. Dr. Wiseman noted, however, that the results should be considered in light of the fact that the Zevalin group’s quality of life was lower at baseline than that of the rituximab group.
Well Tolerated
Zevalin can cause decreasing blood cell counts during the fifth or sixth week of treatment, Dr. Wiseman said. Grade IV hematologic toxicity occurred in about 30% of patients after Zevalin. Although Zevalin is considered a more potent drug than rituximab, the quality-of-life study showed that even such aggressive therapy can be well tolerated. "We know now that Zevalin is well tolerated by patients with low-grade non-Hodgkin’s lymphoma," Dr. Wiseman said.
