TY - JOUR
T1 - Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia
AU - Byrd, J. C.
AU - Brown, J. R.
AU - O'Brien, S.
AU - Barrientos, J. C.
AU - Kay, N. E.
AU - Reddy, N. M.
AU - Coutre, S.
AU - Tam, C. S.
AU - Mulligan, S. P.
AU - Jaeger, U.
AU - Devereux, S.
AU - Barr, P. M.
AU - Furman, R. R.
AU - Kipps, T. J.
AU - Cymbalista, F.
AU - Pocock, C.
AU - Thornton, P.
AU - Caligaris-Cappio, F.
AU - Robak, T.
AU - Delgado, J.
AU - Schuster, S. J.
AU - Montillo, M.
AU - Schuh, A.
AU - De Vos, S.
AU - Gill, D.
AU - Bloor, A.
AU - Dearden, C.
AU - Moreno, C.
AU - Jones, J. J.
AU - Chu, A. D.
AU - Fardis, M.
AU - McGreivy, J.
AU - Clow, F.
AU - James, D. F.
AU - Hillmen, P.
PY - 2014
Y1 - 2014
N2 - BACKGROUND: In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. METHODS: In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. RESULTS: At a median follow-up of 9.4 months, ibrutinib significantly improved progressionfree survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. CONCLUSIONS: Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL.
AB - BACKGROUND: In patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL), a short duration of response to therapy or adverse cytogenetic abnormalities are associated with a poor outcome. We evaluated the efficacy of ibrutinib, a covalent inhibitor of Bruton's tyrosine kinase, in patients at risk for a poor outcome. METHODS: In this multicenter, open-label, phase 3 study, we randomly assigned 391 patients with relapsed or refractory CLL or SLL to receive daily ibrutinib or the anti-CD20 antibody ofatumumab. The primary end point was the duration of progression-free survival, with the duration of overall survival and the overall response rate as secondary end points. RESULTS: At a median follow-up of 9.4 months, ibrutinib significantly improved progressionfree survival; the median duration was not reached in the ibrutinib group (with a rate of progression-free survival of 88% at 6 months), as compared with a median of 8.1 months in the ofatumumab group (hazard ratio for progression or death in the ibrutinib group, 0.22; P<0.001). Ibrutinib also significantly improved overall survival (hazard ratio for death, 0.43; P = 0.005). At 12 months, the overall survival rate was 90% in the ibrutinib group and 81% in the ofatumumab group. The overall response rate was significantly higher in the ibrutinib group than in the ofatumumab group (42.6% vs. 4.1%, P<0.001). An additional 20% of ibrutinib-treated patients had a partial response with lymphocytosis. Similar effects were observed regardless of whether patients had a chromosome 17p13.1 deletion or resistance to purine analogues. The most frequent nonhematologic adverse events were diarrhea, fatigue, pyrexia, and nausea in the ibrutinib group and fatigue, infusion-related reactions, and cough in the ofatumumab group. CONCLUSIONS: Ibrutinib, as compared with ofatumumab, significantly improved progression-free survival, overall survival, and response rate among patients with previously treated CLL or SLL.
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U2 - 10.1056/NEJMoa1400376
DO - 10.1056/NEJMoa1400376
M3 - Article
C2 - 24881631
AN - SCOPUS:84904252369
SN - 0028-4793
VL - 371
SP - 213
EP - 223
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 3
ER -