Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia

J. C. Byrd, J. R. Brown, S. O'Brien, J. C. Barrientos, Neil Elliot Kay, N. M. Reddy, S. Coutre, C. S. Tam, S. P. Mulligan, U. Jaeger, S. Devereux, P. M. Barr, R. R. Furman, T. J. Kipps, F. Cymbalista, C. Pocock, P. Thornton, F. Caligaris-Cappio, T. Robak, J. DelgadoS. J. Schuster, M. Montillo, A. Schuh, S. De Vos, D. Gill, A. Bloor, C. Dearden, C. Moreno, J. J. Jones, A. D. Chu, M. Fardis, J. McGreivy, F. Clow, D. F. James, P. Hillmen

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)213-223
Number of pages11
JournalNew England Journal of Medicine
Volume371
Issue number3
DOIs
StatePublished - 2014

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Lymphoid Leukemia
B-Cell Chronic Lymphocytic Leukemia
Disease-Free Survival
Fatigue
Survival
PCI 32765
ofatumumab
Survival Rate
Lymphocytosis
Chromosome Deletion
Cough
Chromosome Aberrations
Nausea
Anti-Idiotypic Antibodies
Diarrhea
Fever

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Byrd, J. C., Brown, J. R., O'Brien, S., Barrientos, J. C., Kay, N. E., Reddy, N. M., ... Hillmen, P. (2014). Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. New England Journal of Medicine, 371(3), 213-223. https://doi.org/10.1056/NEJMoa1400376

Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. / Byrd, J. C.; Brown, J. R.; O'Brien, S.; Barrientos, J. C.; Kay, Neil Elliot; Reddy, N. M.; Coutre, S.; Tam, C. S.; Mulligan, S. P.; Jaeger, U.; Devereux, S.; Barr, P. M.; Furman, R. R.; Kipps, T. J.; Cymbalista, F.; Pocock, C.; Thornton, P.; Caligaris-Cappio, F.; Robak, T.; Delgado, J.; Schuster, S. J.; Montillo, M.; Schuh, A.; De Vos, S.; Gill, D.; Bloor, A.; Dearden, C.; Moreno, C.; Jones, J. J.; Chu, A. D.; Fardis, M.; McGreivy, J.; Clow, F.; James, D. F.; Hillmen, P.

In: New England Journal of Medicine, Vol. 371, No. 3, 2014, p. 213-223.

Research output: Contribution to journalArticle

Byrd, JC, Brown, JR, O'Brien, S, Barrientos, JC, Kay, NE, Reddy, NM, Coutre, S, Tam, CS, Mulligan, SP, Jaeger, U, Devereux, S, Barr, PM, Furman, RR, Kipps, TJ, Cymbalista, F, Pocock, C, Thornton, P, Caligaris-Cappio, F, Robak, T, Delgado, J, Schuster, SJ, Montillo, M, Schuh, A, De Vos, S, Gill, D, Bloor, A, Dearden, C, Moreno, C, Jones, JJ, Chu, AD, Fardis, M, McGreivy, J, Clow, F, James, DF & Hillmen, P 2014, 'Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia', New England Journal of Medicine, vol. 371, no. 3, pp. 213-223. https://doi.org/10.1056/NEJMoa1400376
Byrd, J. C. ; Brown, J. R. ; O'Brien, S. ; Barrientos, J. C. ; Kay, Neil Elliot ; Reddy, N. M. ; Coutre, S. ; Tam, C. S. ; Mulligan, S. P. ; Jaeger, U. ; Devereux, S. ; Barr, P. M. ; Furman, R. R. ; Kipps, T. J. ; Cymbalista, F. ; Pocock, C. ; Thornton, P. ; Caligaris-Cappio, F. ; Robak, T. ; Delgado, J. ; Schuster, S. J. ; Montillo, M. ; Schuh, A. ; De Vos, S. ; Gill, D. ; Bloor, A. ; Dearden, C. ; Moreno, C. ; Jones, J. J. ; Chu, A. D. ; Fardis, M. ; McGreivy, J. ; Clow, F. ; James, D. F. ; Hillmen, P. / Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. In: New England Journal of Medicine. 2014 ; Vol. 371, No. 3. pp. 213-223.
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abstract = "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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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, Neil Elliot

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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