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Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia

(2015) NEW ENGLAND JOURNAL OF MEDICINE. 373(25). p.2425-2437
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Abstract
BACKGROUND : Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. METHODS : We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. RESULTS : The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P<0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98% with ibrutinib versus 85% with chlorambucil, with a relative risk of death that was 84% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P = 0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86% vs. 35%, P<0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87% of the patients in the ibrutinib group are continuing to take ibrutinib. CONCLUSIONS : Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables.
Keywords
PREVIOUSLY UNTREATED PATIENTS, TYROSINE KINASE, PCI-32765, CANCER, CYCLOPHOSPHAMIDE, CLL, FLUDARABINE, CHLORAMBUCIL, OPEN-LABEL, PHASE-3 TRIAL

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Chicago
Burger, JA, A Tedeschi, PM Barr, T Robak, C Owen, P Ghia, O Bairey, et al. 2015. “Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.” New England Journal of Medicine 373 (25): 2425–2437.
APA
Burger, J., Tedeschi, A., Barr, P., Robak, T., Owen, C., Ghia, P., Bairey, O., et al. (2015). Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. NEW ENGLAND JOURNAL OF MEDICINE, 373(25), 2425–2437.
Vancouver
1.
Burger J, Tedeschi A, Barr P, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. NEW ENGLAND JOURNAL OF MEDICINE. 2015;373(25):2425–37.
MLA
Burger, JA, A Tedeschi, PM Barr, et al. “Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia.” NEW ENGLAND JOURNAL OF MEDICINE 373.25 (2015): 2425–2437. Print.
@article{7076419,
  abstract     = {BACKGROUND : Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma. 
METHODS : We randomly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil. The primary end point was progression-free survival as assessed by an independent review committee. 
RESULTS : The median age of the patients was 73 years. During a median follow-up period of 18.4 months, ibrutinib resulted in significantly longer progression-free survival than did chlorambucil (median, not reached vs. 18.9 months), with a risk of progression or death that was 84\% lower with ibrutinib than that with chlorambucil (hazard ratio, 0.16; P{\textlangle}0.001). Ibrutinib significantly prolonged overall survival; the estimated survival rate at 24 months was 98\% with ibrutinib versus 85\% with chlorambucil, with a relative risk of death that was 84\% lower in the ibrutinib group than in the chlorambucil group (hazard ratio, 0.16; P = 0.001). The overall response rate was higher with ibrutinib than with chlorambucil (86\% vs. 35\%, P{\textlangle}0.001). The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib. Adverse events of any grade that occurred in at least 20\% of the patients receiving ibrutinib included diarrhea, fatigue, cough, and nausea; adverse events occurring in at least 20\% of those receiving chlorambucil included nausea, fatigue, neutropenia, anemia, and vomiting. In the ibrutinib group, four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage. A total of 87\% of the patients in the ibrutinib group are continuing to take ibrutinib. 
CONCLUSIONS : Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma, as assessed by progression-free survival, overall survival, response rate, and improvement in hematologic variables.},
  author       = {Burger, JA and Tedeschi, A and Barr, PM and Robak, T and Owen, C and Ghia, P and Bairey, O and Hillmen, P and Bartlett, NL and Li, J and Simpson, D and Grosicki, S and Devereux, S and McCarthy, H and Coutre, S and Quach, H and Gaidano, G and Maslyak, Z and Stevens, DA and Janssens, A and Offner, Fritz and Mayer, J and O'Dwyer, M and Hellmann, A and Schuh, A and Siddiqi, T and Polliack, A and Tam, CS and Suri, D and Cheng, M and Clow, F and Styles, L and James, DF and Kipps, TJ},
  issn         = {0028-4793},
  journal      = {NEW ENGLAND JOURNAL OF MEDICINE},
  language     = {eng},
  number       = {25},
  pages        = {2425--2437},
  title        = {Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia},
  url          = {http://dx.doi.org/10.1056/NEJMoa1509388},
  volume       = {373},
  year         = {2015},
}

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