December 14, 2011 — For patients with low-tumor-burden follicular lymphoma, new data suggest that treatment with rituximab (Rituxan, Genentech) is better than a "watch-and-wait" strategy. In addition, outcomes with rituximab given only on disease progression (a retreatment strategy) and with rituximab given as maintenance therapy are similar, but the retreatment strategy requires nearly 4 times less drug.
These data were presented here at the American Society of Hematology 53rd Annual Meeting by Brad Kahl, MD, assistant professor of medicine at the University of Wisconsin in Madison.
"We believe the retreatment strategy is the preferred option to help patients with low-tumor-burden follicular lymphoma manage their disease," Dr. Kahl said. There was no difference in the treatment outcomes between the 2 strategies, but the retreatment strategy is less costly, he noted.
Patients With Few Symptoms
Historically, patients with low-tumor-burden follicular lymphoma, in which patients have limited or no symptoms, are usually not treated immediately, but are followed with a watch-and-wait strategy, Dr. Kahl explained.
Several older trials that looked at giving chemotherapy early in these patients failed to show an overall survival advantage, so watch and wait is considered a reasonable standard, he said. Such an approach allows patients a delay of about 3 years before they are started on chemotherapy.
However, there have been hints from other trials that using targeted rituximab therapy early on could delay the start of chemotherapy even further, and provide superior disease control. A previous study showed that maintenance therapy with rituximab was superior to observation in this regard, Dr. Kahl explained.
When his team began their study, they expected maintenance rituximab to be superior to the retreatment strategy. In fact, both had similar outcomes.
RESORT Results
The phase 3 study, known as RESORT (Results of Eastern Cooperative Oncology Group Protocol E4402), enrolled 384 patients, all of whom were treated with rituximab 375 mg/m² weekly for 4 weeks.
Those who responded to rituximab (274 patients; 71%) continued with the drug, but were randomized to receive it regularly as maintenance therapy (a single dose of rituximab every 3 months) or in a retreatment strategy (4 weekly doses of rituximab at disease progression).
Over 3 years, the maintenance group received a median of 15.5 doses (range, 5 to 31) per patient, whereas the retreatment group received an median of 4 doses (range, 4 to 16) per patient.
The time to treatment failure, at which point patients moved on to chemotherapy, was 3.9 years in the maintenance group and 3.6 years in the retreatment group. The difference between the 2 groups was not statistically significant, and both groups were better than the 3 years historically seen with the watch-and-wait strategy, Dr. Kahl noted.
At 3-year follow-up, 95% of patients in the maintenance group and 86% in the retreatment group remained free from chemotherapy, he added.
Rituximab was well tolerated, he said, and less than 5% of patients experienced any severe toxicities. However, there were more serious adverse events in the maintenance group than in the retreatment group (7 vs 1), and more patients withdrew from the trial (26 vs 16).
Dr. Kahl and colleagues had wondered whether the retreatment strategy, in which the patient goes into remission and then progresses before being retreated, could be potentially more stressful for patients than the maintenance strategy, where they receive regular treatment. However, assessment of quality of life and anxiety at 12 months found no differences between the 2 groups.
Given the excellent outcomes, the fewer adverse events, the lack of difference on quality of life, and the fewer doses of rituximab used, Dr. Kahl concluded that rituximab retreatment is "our recommended strategy if electing to use rituximab,."
However, he noted that it remains unclear which strategy — watch and wait, rituximab alone, or rituximab plus chemotherapy — is the best strategy for the end point of overall survival. "That will require another study," he said.
Commenting on these data for Medscape Medical News, Jane Winter, MD, professor of medicine in the division of hematology/oncology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, said that she will be analyzing these results and is eager to see longer follow-up data. "I was a watch and waiter, but now I'm in transition," she said.
The fact that retreatment was just as good as maintenance goes against what was expected, she noted. "We became convinced some time ago that maintenance was the way to go."
These results are important because they show that the outcomes with retreatment are very similar, yet this strategy reduces the frequency of treatment and the costs.
"If we can limit the frequency of treatment or reduce the need for chemotherapy and still maintain good outcomes, we can reduce some of the burdens on both the patients and the healthcare community," she said in a statement. Dr. Winter was moderator of a press conference during which the findings were highlighted.
American Society of Hematology (ASH) 53rd Annual Meeting: Abstract LBA-6. Presented December 13, 2011.
These data were presented here at the American Society of Hematology 53rd Annual Meeting by Brad Kahl, MD, assistant professor of medicine at the University of Wisconsin in Madison.
"We believe the retreatment strategy is the preferred option to help patients with low-tumor-burden follicular lymphoma manage their disease," Dr. Kahl said. There was no difference in the treatment outcomes between the 2 strategies, but the retreatment strategy is less costly, he noted.
Patients With Few Symptoms
Historically, patients with low-tumor-burden follicular lymphoma, in which patients have limited or no symptoms, are usually not treated immediately, but are followed with a watch-and-wait strategy, Dr. Kahl explained.
Several older trials that looked at giving chemotherapy early in these patients failed to show an overall survival advantage, so watch and wait is considered a reasonable standard, he said. Such an approach allows patients a delay of about 3 years before they are started on chemotherapy.
However, there have been hints from other trials that using targeted rituximab therapy early on could delay the start of chemotherapy even further, and provide superior disease control. A previous study showed that maintenance therapy with rituximab was superior to observation in this regard, Dr. Kahl explained.
When his team began their study, they expected maintenance rituximab to be superior to the retreatment strategy. In fact, both had similar outcomes.
RESORT Results
The phase 3 study, known as RESORT (Results of Eastern Cooperative Oncology Group Protocol E4402), enrolled 384 patients, all of whom were treated with rituximab 375 mg/m² weekly for 4 weeks.
Those who responded to rituximab (274 patients; 71%) continued with the drug, but were randomized to receive it regularly as maintenance therapy (a single dose of rituximab every 3 months) or in a retreatment strategy (4 weekly doses of rituximab at disease progression).
Over 3 years, the maintenance group received a median of 15.5 doses (range, 5 to 31) per patient, whereas the retreatment group received an median of 4 doses (range, 4 to 16) per patient.
The time to treatment failure, at which point patients moved on to chemotherapy, was 3.9 years in the maintenance group and 3.6 years in the retreatment group. The difference between the 2 groups was not statistically significant, and both groups were better than the 3 years historically seen with the watch-and-wait strategy, Dr. Kahl noted.
At 3-year follow-up, 95% of patients in the maintenance group and 86% in the retreatment group remained free from chemotherapy, he added.
Rituximab was well tolerated, he said, and less than 5% of patients experienced any severe toxicities. However, there were more serious adverse events in the maintenance group than in the retreatment group (7 vs 1), and more patients withdrew from the trial (26 vs 16).
Dr. Kahl and colleagues had wondered whether the retreatment strategy, in which the patient goes into remission and then progresses before being retreated, could be potentially more stressful for patients than the maintenance strategy, where they receive regular treatment. However, assessment of quality of life and anxiety at 12 months found no differences between the 2 groups.
Given the excellent outcomes, the fewer adverse events, the lack of difference on quality of life, and the fewer doses of rituximab used, Dr. Kahl concluded that rituximab retreatment is "our recommended strategy if electing to use rituximab,."
However, he noted that it remains unclear which strategy — watch and wait, rituximab alone, or rituximab plus chemotherapy — is the best strategy for the end point of overall survival. "That will require another study," he said.
Commenting on these data for Medscape Medical News, Jane Winter, MD, professor of medicine in the division of hematology/oncology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, said that she will be analyzing these results and is eager to see longer follow-up data. "I was a watch and waiter, but now I'm in transition," she said.
The fact that retreatment was just as good as maintenance goes against what was expected, she noted. "We became convinced some time ago that maintenance was the way to go."
These results are important because they show that the outcomes with retreatment are very similar, yet this strategy reduces the frequency of treatment and the costs.
"If we can limit the frequency of treatment or reduce the need for chemotherapy and still maintain good outcomes, we can reduce some of the burdens on both the patients and the healthcare community," she said in a statement. Dr. Winter was moderator of a press conference during which the findings were highlighted.
American Society of Hematology (ASH) 53rd Annual Meeting: Abstract LBA-6. Presented December 13, 2011.
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