CHICAGO – After 2 years of maintenance immunotherapy with rituximab, elderly patients with chronic lymphocytic leukemia had better rates of progression-free survival than did patients in an observation group, based on results of the CLL 2007 SA trial from the French FILO (French Innovative Leukemia Organisation) Group.
The two groups did not significantly differ in overall survival, however, with 92.6% estimated 3-year overall survival in the rituximab group and 87.2% in the observation group. Further, the patients given rituximab had more adverse events, based on data presented by Dr. Caroline Dartigeas of the University Hospital in Tours, France, at the annual meeting of the American Society of Clinical Oncology.
Given the cost and risk for events with rituximab, the findings raise the question of whether there are any meaningful benefits for maintenance rituximab after induction therapy, Dr. Jonathan W. Friedberg of the University of Rochester, N.Y., who was the discussant of the paper, remarked after the presentation. He asked whether there is any evidence that patients feel better if they’re in remission and, thus, their quality of life is improved.
The study included fit, treatment-naive patients aged 65 years and older with B-cell CLL who lacked del17p. Median patient age was 71.3 years, and two-thirds of the patients were men.
Patients received four cycles of induction therapy with fludarabine, cyclophosphamide, and rituximab on a shortened schedule chosen to reduce the risk of cumulative toxicity. At randomization, patients were stratified for immunoglobulin heavy chain variable (IGHV) status (54.8% of patients had unmutated status) and del11q (21.3% of patients had the deletion). Patients who had complete (25.7% of patients) or partial (62.8% of patients) responses were randomly allocated to either maintenance rituximab (202 patients given 500 mg/m2 twice per month for 2 years) or to observation (207 patients). Median follow-up from randomization was 43.6 months.
Median progression-free survival in the rituximab arm was 59.3 months (95% confidence interval, 49.6; not reached), compared with 49 months (95% CI, 40.9-60.5) in the observation group (hazard ratio, 0.597; 95% CI, 0.437-0.814; P = .0011), corresponding to 3-year progression-free survival of 83% and 64.2% in each arm, respectively.
Estimated overall survival at 3 years was 92.6% with rituximab maintenance and 87.2% in the observation group. Rituximab maintenance significantly improved progression-free survival in patients with and without del11q and in those with unmutated IGHV.
Serious adverse events for hematologic toxicity were seen in 6.9% of rituximab-treated patients and 1.9% of patients in the observation group (P = .027). Serious adverse events for infectious toxicity occurred in 18.8% of rituximab-treated patients and 10.1% of the observation group (P = .036). There were 69 deaths post randomization: 32 in the rituximab-treated group and 37 in the observation group. Secondary cancers, excluding basal cell carcinomas of the skin, occurred in 15.3% of the rituximab arm, including five cases of myelodysplastic syndrome, and in 11.1% of the observation group, including three cases of myelodysplastic syndrome.
Dr. Dartigeas is a consultant to Gilead Sciences and has provided expert testimony for Roche/Genentech. Genentech and Biogen jointly market rituximab (Rituxan).
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