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

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• 作者：Thomas  ; Elter DrMD^a ;   ; ^{thomas.elter@uk-koeln.de} ; Liana  ; Gercheva-Kyuchukova ProfMD^b ; Halyna  ; Pylylpenko MD^c ; Tadesuz  ; Robak ProfMD^d ; Branimir  ; Jaksic ProfMD^e ; Grigoriy  ; Rekhtman MD^f ; S?awomira  ; Kyrcz-Krzemie¨½ ProfMD^g ; Mykola  ; Vatutin MD^h ; Jingyang  ; Wu MSⁱ ; Cynthia  ; Sirard MDⁱ ; Michael  ; Hallek ProfMD^a ;   ; ^j ; Andreas  ; Engert ProfMD^a
• 刊名：Lancet Oncology
• 出版年：2011
• 出版时间：December 2011
• 年：2011
• 卷：12
• 期：13
• 页码：1204-1213
• 全文大小：286 K

文摘

Summary

Background

Chronic lymphocytic leukaemia (CLL) is an incurable and chronic disorder, with worsening prognosis for patients as their disease progresses. We compared the efficacy and safety of the combination of fludarabine and alemtuzumab with fludarabine monotherapy in previously treated patients with relapsed or refractory CLL.

Methods

Patients (aged ?8 years) with CLL Binet stage A, B, or C or Rai stages I¨CIV 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?) or monotherapy (fludarabine 25 mg/m² on days 1?) by use of an interactive voice response system. Both regimens were given intravenously for a maximum of six 28-day cycles. The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with , number .

Findings

Fludarabine plus alemtuzumab (n=168) resulted in better PFS than did fludarabine monotherapy (n=167; median 23¡¤7 months [95 % CI 19¡¤2?8¡¤4] vs 16¡¤5 months [12¡¤5?1¡¤2]; hazard ratio 0¡¤61 [95 % CI 0¡¤47?¡¤80]; p=0¡¤0003) and overall survival (median not reached vs 52¡¤9 months [40¡¤9¨Cnot reached]; 0¡¤65 [0¡¤45?¡¤94]; p=0¡¤021) compared with fludarabine alone. All-cause adverse events occurred in 161 (98 % ) of 164 patients in the combination treatment group and 149 (90 % ) of 165 in the fludarabine alone group. Patients in the 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 the 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). The incidence of serious adverse events was higher in the combination treatment group (54 [33 % ] of 164 vs 41 [25 % ] of 165); deaths due to adverse events were similar between the two groups (ten [6 % ] vs 12 [7 % ]).

Interpretation

The combination of fludarabine and alemtuzumab is another treatment option for patients with previously treated CLL.

Funding

Genzyme.