December 12, 2002

Jane Salodof MacNeil

Dec. 12, 2002 (Philadelphia) -- Long-term follow-up of five clinical trials has found that 70% of advanced non-Hodgkin's lymphoma (NHL) patients who had a complete response to tositumomab and the experimental monoclonal antibody I-131 tositumomab (Bexxar) were still alive and disease-free after more than seven years.

A total of 250 high-risk patients participated in the studies, which began in 1990. All had relapsed or refractory low-grade or transformed low-grade NHL. Two-thirds had bulky disease. More than half had failed four or more prior regimens. Nearly half had bone marrow involvement.

Fifty-six percent of patients responded to the radioimmunotherapy, and the median duration of response was 14.7 months. These numbers include 30% of patients who had a confirmed complete response for which the median duration, 58 months, has yet to be reached.

"Study after study has shown that a durable response can be obtained in a significant portion of the patients going out to follow-up after eight years," principal investigator Mark S. Kaminski, MD, from the University of Michigan Medical Center in Ann Arbor, told Medscape here at the American Society of Hematology (ASH) annual meeting.

No other treatment has produced as durable a response, he said, adding, "It's well tolerated. It can be given in the outpatient setting, and it's a one-time treatment."

The U.S. Food and Drug Administration (FDA) has scheduled a meeting for Dec. 17 on an application by Corixia, the Seattle-based biotech firm seeking approval of tositumomab for treatment of advanced NHL. The FDA had initially rejected the application, saying it needed more safety information, but reversed itself earlier this month.

Consequently, physicians and stock analysts swarmed Dr. Kaminski and another poster presenter, Sandra Horning, MD, of Stanford University Medical School, who reported that the same radioimmunotherapy combination produced durable responses in indolent NHL patients, whose disease had progressed after treatment with rituximab. In her study, 68% of 40 patients responded, and 30% had a complete response. Fourteen patients had a durable response, defined as a year or more.

The same question was asked repeatedly: How did the data on the posters compare with published data for ibritumomab tiuxetan (Zevalin), a monoclonal antibody already approved by the FDA?

"I cannot believe [tositumomab] is inferior, and it must be superior," Gary Spitzer, MD, from Cancer Centers Carolinas in Greenville, South Carolina, told Medscape, cautioning that he could not be sure, however. "It's an incredible molecule. They just can't tell you objectively, without a randomized trial, which is superior."

"The question is best answered if the two [monoclonal antibodies] are out there and available," Dr. Horning said, adding that a phase III study will compare CHOP to CHOP followed by tositumomab.

Similarly, Dr. Kaminski said the best test would be to have the new antibody approved and available. He predicted it also would be used for front-line treatment of NHL. The data on response rates and durability of response is comparable to the most aggressive chemotherapies without the adverse effects, he said. "Whether it's better or not will have to be tested."

ASH 44th Annual Meeting: Abstracts 1381 and 1385. Presented Dec. 7, 2002.

Reviewed by Gary D. Vogin, MD

Jane Salodof MacNeil is a freelance writer for Medscape.

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