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No Significant Difference in Time to Treatment Failure With Rituximab Retreatment vs Maintenance in Low-Tumor-Burden Follicular Lymphoma

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Key Points

  • There was no significant difference in time to treatment failure for retreatment vs maintenance rituximab.
  • The maintenance strategy was associated with prolonged time to first cytotoxic chemotherapy.

Maintenance rituximab (Rituxan) has been shown to improve progression-free survival vs observation in low-tumor-burden follicular lymphoma. In the Eastern Cooperative Oncology Group (ECOG) E4402 Trial (RESORT), reported in the Journal of Clinical Oncology, Kahl et al found no significant difference in time to treatment failure with a strategy of rituximab retreatment at progression vs rituximab maintenance in patients with previously untreated low-tumor-burden follicular lymphoma. The maintenance strategy was associated with longer time to first cytotoxic chemotherapy and the retreatment strategy required less use of rituximab.

Study Details

In the trial, 408 patients with previously untreated low-tumor-burden follicular lymphoma received four weekly doses of rituximab at 375 mg/m2 and those with complete or partial response at week 13 (n = 289) were randomly assigned to rituximab maintenance (n = 146) or retreatment (n = 143). Rituximab maintenance consisted of a single dose of rituximab every 3 months until treatment failure. Retreatment consisted of retreatment at each disease progression until treatment failure.

Patients were evaluated every 13 weeks and underwent repeat computed tomography scans every 26 weeks. The primary endpoint was time to treatment failure.

The retreatment and maintenance groups were generally balanced for age (median, 60 and 59 years), sex (53% and 55% female), race (94% and 95% white), ECOG performance status (0 in 84% and 88%), bone marrow involvement (43% and 50%), elevated lactate dehydrogenase (13% and 15%), elevated β2-microglobulin (46% and 38%), stage (III in 55% and 46%, IV in 44% and 53%), Follicular Lymphoma International Prognostic Index score (low in 15% and 16%, intermediate in 45% in both, high in 40% and 39%), histology grade (1 in 71% and 66%, 2 in 23% and 29%, 3a in 2% and 1%), and time from diagnosis < 1 year (92% and 90%).

Time to Treatment Failure

After median follow-up of 4.5 years, there were 80 treatment failures in the retreatment group and 78 in the maintenance group. Median time to treatment failure was 3.9 vs 4.3 years (P = .54), with 61% vs 64% of patients remaining free of treatment failure at 3 years (P = .33).

In a sensitivity analysis censoring patient withdrawals for nonmedical reasons, estimated treatment failure-free survival was 65% vs 73% at 3 years (P = .16) and 50% vs 53% at 5 years. There was no difference in risk for treatment failure according to retreatment vs maintenance on multivariate analysis (hazard ratio = 1.07, P = .68).

Other Outcomes

As expected, progression-free survival was better in the maintenance group (50% vs 78% at 3 years). There were few deaths and overall survival did not differ between groups (94% vs 94% at 5 years). Rates of freedom from cytotoxic chemotherapy at 3 years were 84% vs 95% (P = .03). Including the four induction doses, the median number of rituximab doses was four (range, 4–16) in the retreatment group and 18 (range, 5–35) in the maintenance group. There were no differences in health-related quality of life or anxiety between the two groups.

Toxicity

Grade ≥ 3 adverse events were infrequent in both groups. Four grade 3 events occurred in retreatment patients and 10 occurred in maintenance patients, two grade 4 events occurred in retreatment patients, and one grade 5 event occurred in a maintenance patient.

The investigators concluded: “In low–tumor burden [follicular lymphoma], a retreatment strategy uses less rituximab while providing disease control comparable to that achieved with a maintenance strategy.”

They noted: “There was a small advantage for [maintenance rituximab] in time to first cytotoxic therapy, but significantly more rituximab was required to achieve this benefit. This trial has implications for both research and practice. With regard to research, it would be highly interesting to determine if a [retreatment] strategy could produce outcomes comparable to those of a [maintenance] strategy, when applied after rituximab plus chemotherapy in high–tumor burden [follicular lymphoma]. Given the widespread use of [maintenance rituximab], the resource use implications are large. With regard to practice, RESORT indicates that if opting for single-agent rituximab as initial therapy for low–tumor burden [follicular lymphoma], a strategy of re-treatment at disease progression is recommended over a strategy of continuous maintenance therapy.”

Brad S. Kahl, MD, of University of Wisconsin School of Medicine and Public Health, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by grants from the National Cancer Institute, National Institutes of Health, and Department of Health and Human Services. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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