Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukemia: A randomised phase 3 trial

The Lancet Oncology, 10/12/2011

Elter T et al. – The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL.

Methods

  • Patients (aged ≥18 years) with CLL Binet stage A, B, or C or Rai stages I—IV were randomly assigned in a 1:1 ratio according to a computer-generated allocation schedule to open-label combination treatment (fludarabine 30 mg/m2 per day and alemtuzumab 30 mg per day on days 1—3) or monotherapy (fludarabine 25 mg/m2 on days 1—5) by use of an interactive voice response system
  • Both regimens were given intravenously for a maximum of six 28-day cycles
  • Primary endpoint was PFS
  • Analysis was by intention to treat

Results

  • Fludarabine plus alemtuzumab (n=168) resulted in better PFS than did fludarabine monotherapy (n=167; median 23·7 months [95% CI 19·2—28·4] vs 16·5 months [12·5—21·2]; HR 0·61 [95% CI 0·47—0·80]; p=0·0003) and OS (median not reached vs 52·9 months [40·9—not reached]; 0·65 [0·45—0·94]; p=0·021) compared with fludarabine alone
  • All-cause AEs occurred in 161 (98%) of 164 patients in combination treatment group and 149 (90%) of 165 in the fludarabine alone group
  • Patients in fludarabine plus alemtuzumab group had more cytomegalovirus events (23 [14%] vs one [<1%]) and grade 1 or 2 potentially alemtuzumab infusion-related adverse reactions (102 [62%] vs 22 [13%])
  • Grade 3 or 4 toxicities in combination treatment and monotherapy groups were leucopenia (121 [74%] of 164 vs 55 [34%] of 164), lymphopenia (149 [94%] of 158 vs 53 [33%] of 161), neutropenia (93 [59%] of 157 vs 110 [68%] of 161), thrombocytopenia (18 [11%] of 164 vs 27 [17%] of 163), and anaemia (14 [9%] of 163 vs 28 [17%] of 164)
  • Incidence of serious AEs was higher in combination treatment group (54 [33%] of 164 vs 41 [25%] of 165); deaths due to AEs were similar between 2 groups (10 [6%] vs 12 [7%])

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