Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

Giuseppe Saglio, Dong Wook Kim, Surapol Issaragrisil, Philipp Le Coutre, Gabriel Etienne, Clarisse Lobo, Ricardo Pasquini, Richard E. Clark, Andreas Hochhaus, Timothy P. Hughes, Neil Gallagher, Albert Hoenekopp, Mei Dong, Ariful Haque, Richard A. Larson, Hagop M. Kantarjian

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Abstract

BACKGROUND: Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. METHODS: In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months. RESULTS: At 12 months, the rates of major molecular response for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice that for imatinib (22%) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P=0.01 and P=0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups. CONCLUSIONS: Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.)

LanguageEnglish
Pages2251-2259
Number of pages9
JournalNew England Journal of Medicine
Volume362
Issue number24
DOIs
Publication statusPublished - 17 Jun 2010

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Saglio, G., Kim, D. W., Issaragrisil, S., Le Coutre, P., Etienne, G., Lobo, C., ... Kantarjian, H. M. (2010). Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. New England Journal of Medicine, 362(24), 2251-2259. https://doi.org/10.1056/NEJMoa0912614
Saglio, Giuseppe ; Kim, Dong Wook ; Issaragrisil, Surapol ; Le Coutre, Philipp ; Etienne, Gabriel ; Lobo, Clarisse ; Pasquini, Ricardo ; Clark, Richard E. ; Hochhaus, Andreas ; Hughes, Timothy P. ; Gallagher, Neil ; Hoenekopp, Albert ; Dong, Mei ; Haque, Ariful ; Larson, Richard A. ; Kantarjian, Hagop M. / Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. In: New England Journal of Medicine. 2010 ; Vol. 362, No. 24. pp. 2251-2259.
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abstract = "BACKGROUND: Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. METHODS: In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months. RESULTS: At 12 months, the rates of major molecular response for nilotinib (44{\%} for the 300-mg dose and 43{\%} for the 400-mg dose) were nearly twice that for imatinib (22{\%}) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80{\%} for the 300-mg dose and 78{\%} for the 400-mg dose) than for imatinib (65{\%}) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P=0.01 and P=0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups. CONCLUSIONS: Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.)",
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Saglio, G, Kim, DW, Issaragrisil, S, Le Coutre, P, Etienne, G, Lobo, C, Pasquini, R, Clark, RE, Hochhaus, A, Hughes, TP, Gallagher, N, Hoenekopp, A, Dong, M, Haque, A, Larson, RA & Kantarjian, HM 2010, 'Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia', New England Journal of Medicine, vol. 362, no. 24, pp. 2251-2259. https://doi.org/10.1056/NEJMoa0912614

Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. / Saglio, Giuseppe; Kim, Dong Wook; Issaragrisil, Surapol; Le Coutre, Philipp; Etienne, Gabriel; Lobo, Clarisse; Pasquini, Ricardo; Clark, Richard E.; Hochhaus, Andreas; Hughes, Timothy P.; Gallagher, Neil; Hoenekopp, Albert; Dong, Mei; Haque, Ariful; Larson, Richard A.; Kantarjian, Hagop M.

In: New England Journal of Medicine, Vol. 362, No. 24, 17.06.2010, p. 2251-2259.

Research output: Contribution to journalArticle

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T1 - Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia

AU - Saglio, Giuseppe

AU - Kim, Dong Wook

AU - Issaragrisil, Surapol

AU - Le Coutre, Philipp

AU - Etienne, Gabriel

AU - Lobo, Clarisse

AU - Pasquini, Ricardo

AU - Clark, Richard E.

AU - Hochhaus, Andreas

AU - Hughes, Timothy P.

AU - Gallagher, Neil

AU - Hoenekopp, Albert

AU - Dong, Mei

AU - Haque, Ariful

AU - Larson, Richard A.

AU - Kantarjian, Hagop M.

PY - 2010/6/17

Y1 - 2010/6/17

N2 - BACKGROUND: Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. METHODS: In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months. RESULTS: At 12 months, the rates of major molecular response for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice that for imatinib (22%) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P=0.01 and P=0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups. CONCLUSIONS: Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.)

AB - BACKGROUND: Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib. We evaluated the efficacy and safety of nilotinib, as compared with imatinib, in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (CML) in the chronic phase. METHODS: In this phase 3, randomized, open-label, multicenter study, we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib (at a dose of either 300 mg or 400 mg twice daily) or imatinib (at a dose of 400 mg once daily). The primary end point was the rate of major molecular response at 12 months. RESULTS: At 12 months, the rates of major molecular response for nilotinib (44% for the 300-mg dose and 43% for the 400-mg dose) were nearly twice that for imatinib (22%) (P<0.001 for both comparisons). The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib (80% for the 300-mg dose and 78% for the 400-mg dose) than for imatinib (65%) (P<0.001 for both comparisons). Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase or blast crisis, as compared with those receiving imatinib (P=0.01 and P=0.004, respectively). No patient with progression to the accelerated phase or blast crisis had a major molecular response. Gastrointestinal and fluid-retention events were more frequent among patients receiving imatinib, whereas dermatologic events and headache were more frequent in those receiving nilotinib. Discontinuations due to aminotransferase and bilirubin elevations were low in all three study groups. CONCLUSIONS: Nilotinib at a dose of either 300 mg or 400 mg twice daily was superior to imatinib in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML. (ClinicalTrials.gov number, NCT00471497.)

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DO - 10.1056/NEJMoa0912614

M3 - Article

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JO - New England Journal of Medicine

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Saglio G, Kim DW, Issaragrisil S, Le Coutre P, Etienne G, Lobo C et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. New England Journal of Medicine. 2010 Jun 17;362(24):2251-2259. https://doi.org/10.1056/NEJMoa0912614