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Maintenance therapy with rituximab extends PFS in patients with CLL
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Patients with B-cell chronic lymphocytic leukemia treated with maintenance rituximab following first-line, truncated therapy with fludarabine, cyclophosphamide and rituximab achieved improved PFS compared with patients who underwent observation alone, according to study results presented at the ASCO Annual Meeting.
Maintenance treatment with immunotherapy is “a promising concept to improve outcomes” related to quality and duration of response in CLL, the researchers wrote.
Caroline Dartigeas, MD, of the CHU Bretonneau in Tours, France, and colleagues enrolled treatment-naive patients with B-cell CLL and no deletion of chromosome 17p aged 65 years and over. Treatment with fludarabine, cyclophosphamide and rituximab was shortened from six cycles to four “to reduce the risk of cumulative toxicity in elderly patients with physiological decline,” according to the study abstract.
Patients were then randomly assigned to maintenance therapy with 500 mg/m2 rituximab every 2 months for 2 years or observation. The researchers stratified patients based on 11q chromosome deletion, IGHV status and response at the time of randomization. The primary objective was to demonstrate an improvement in 3-year PFS of 50% in the observation arm and 66% in the rituximab arm.
Four hundred and nine patients (median age 71.3 years; 66.3% men) were included in the analysis (rituximab, n = 202; observation, n = 207). Unmutated IGHV was observed in 54.8% of patients and 21.3% had 11q chromosome deletions. Median follow-up was 43.6 months.
Following treatment with fludarabine, cyclophosphamide and rituximab, 11% of patients achieved complete remission or complete remission with incomplete hematologic recovery, and 62.8% achieved a partial response. Median PFS among patients in the rituximab arm was 59.3 months (95% CI, 49.6-not reached) compared with 49 months (95% CI, 40.9-60.5) in the observation arm (HR, 0.59; 95% CI, 0.43-0.81). This corresponded to a 3-year PFS of 83.0% and 64.2% in each arm, respectively. Three-year OS was estimated to be 92.6% in the rituximab arm and 87.2% in the observation arm.
Maintenance therapy with rituximab “significantly improved PFS” among patients with or without 11q chromosome deletions and in those without mutated IGHV, according to the study results.
Serious adverse events related to hematologic toxicity were reported in 6.9% of patients in the rituximab arm and 1.9% of patients in the observation arm (P = .027). Serious adverse events related to infectious toxicity were reported in 18.8% of patients in the rituximab arm and in 10.1% of patients in the observation arm (P = .036).
Sixty-nine patients died during the study (rituximab, n = 32; observation, n = 37). Secondary cancers, excluding basal cell carcinoma, were reported in 15.3% of patients in the rituximab arm — including five cases of myelodysplastic syndrome — and 11.1% of patients in the observation arm, including three cases of myelodysplastic syndrome.
“Two-year maintenance [with] rituximab significantly improved PFS as compared with observation in select elderly patients with CLL,” the researchers wrote. “This benefit was also observed in patients with unfavorable characteristics. Maintenance was feasible but associated with a higher incidence of toxic events. Benefit from maintenance will be further analyzed according to minimal residual disease eradication.” – by Julia Ernst, MS
Reference:
Dartigeas C, et al. Abstract 7505. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosures: The researchers report no relevant financial disclosures.
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Kanti R. Rai, MD
This was a large, randomized study that was done very well. Elderly patients with CLL were treated with fludarabine, cyclophosphamide and rituximab in a truncated cycle — using four cycles instead of six — followed by randomization to maintenance therapy with rituximab or observation only. The idea was that, perhaps, maintenance rituximab would lead to a long-term benefit.
The results demonstrated that, although PFS with rituximab maintenance was significantly better than observation alone, OS was not significantly different. Therefore, the bottom line is that maintenance with rituximab is not necessary after fludarabine, cyclophosphamide and rituximab in front-line treatment.
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