Improved survival in chronic lymphocytic leukemia

Progression-free survival was improved in patients with chronic lymphocytic leukemia (CLL) who receive the combination of rituximab, fludarabine, and cyclophosphamide. Results of the phase III REACH study demonstrated a median improvement in progression-free survival of 10 months when compared with fludarabine and cyclophosphamide alone. In addition, complete response rates in patients with relapsed or refractory CLL almost doubled with rituximab, fludarabine, and cyclophosphamide compared with fludarabine and cyclophosphamide alone.

In this randomized trial, 552 patients with relapsed or refractory CLL received six 28-day cycles of fludarabine (25 mg/m2 IV on days 1 to 3) and cyclophosphamide (250 mg/m2 IV on days 1 to 3) alone or in combination with rituximab (375 mg/ m2 IV at the start of the first cycle and 500 mg/m2 on day 1 for all subsequent cycles). Progression-free survival was the primary end point. Patients had received a median of one prior treatment regimen: 66% had received a single-agent alkylator therapy, 16% had received a purine analog therapy, and 18% had received combination chemotherapy treatments.

For patients in the rituximab, fludarabine, and cyclophosphamide arm, progression- free survival averaged 30.6 months compared with 20.6 months in the fludarabine and cyclophosphamide arm (P=.0002). The overall response rate was 69.9% in the rituximab arm, significantly higher than the 58% overall response rate in the fludarabine and cyclophosphamide arm (P=.0034). Contributing to this result were the superior complete response rates for patients who received rituximab compared with those who did not (24.3% vs 13%, respectively; P=.0007).

Grade 3 and 4 adverse events were more prevalent in the rituximab, fludarabine, and cyclophosphamide arm versus the fludarabine and cyclophosphamide arm (80% vs 74%), but serious adverse events were similar in each arm (50% vs 48%).

Sources: http://ash.confex.com/ash/2008/webprogram/Paper15742.html; http://www.hemonctoday.com/article.aspx?rid=33462.