Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

Stephen G. O'Brien, François Guilhot, Richard A. Larson, Insa Gathmann, Michele Baccarani, Francisco Cervantes, Jan J. Cornelissen, Thomas Fischer, Andreas Hochhaus, Timothy Hughes, Klaus Lechner, Johan L. Nielsen, Philippe Rousselot, Josy Reiffers, Giuseppe Saglio, John Shepherd, Bengt Simonsson, Alois Gratwohl, John M. Goldman, Hagop Kantarjian & 5 others Kerry Taylor, Gregor Verhoef, Ann E. Bolton, Renaud Capdeville, Brian J. Druker

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Abstract

BACKGROUND: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. METHODS: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. RESULTS After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy. CONCLUSIONS: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.

LanguageEnglish
Pages994-1004
Number of pages11
JournalNew England Journal of Medicine
Volume348
Issue number11
DOIs
Publication statusPublished - 13 Mar 2003

ASJC Scopus subject areas

  • Medicine(all)

Cite this

O'Brien, S. G., Guilhot, F., Larson, R. A., Gathmann, I., Baccarani, M., Cervantes, F., ... Druker, B. J. (2003). Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. New England Journal of Medicine, 348(11), 994-1004. https://doi.org/10.1056/NEJMoa022457
O'Brien, Stephen G. ; Guilhot, François ; Larson, Richard A. ; Gathmann, Insa ; Baccarani, Michele ; Cervantes, Francisco ; Cornelissen, Jan J. ; Fischer, Thomas ; Hochhaus, Andreas ; Hughes, Timothy ; Lechner, Klaus ; Nielsen, Johan L. ; Rousselot, Philippe ; Reiffers, Josy ; Saglio, Giuseppe ; Shepherd, John ; Simonsson, Bengt ; Gratwohl, Alois ; Goldman, John M. ; Kantarjian, Hagop ; Taylor, Kerry ; Verhoef, Gregor ; Bolton, Ann E. ; Capdeville, Renaud ; Druker, Brian J. / Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. In: New England Journal of Medicine. 2003 ; Vol. 348, No. 11. pp. 994-1004.
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abstract = "BACKGROUND: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. METHODS: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. RESULTS After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy. CONCLUSIONS: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.",
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O'Brien, SG, Guilhot, F, Larson, RA, Gathmann, I, Baccarani, M, Cervantes, F, Cornelissen, JJ, Fischer, T, Hochhaus, A, Hughes, T, Lechner, K, Nielsen, JL, Rousselot, P, Reiffers, J, Saglio, G, Shepherd, J, Simonsson, B, Gratwohl, A, Goldman, JM, Kantarjian, H, Taylor, K, Verhoef, G, Bolton, AE, Capdeville, R & Druker, BJ 2003, 'Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia', New England Journal of Medicine, vol. 348, no. 11, pp. 994-1004. https://doi.org/10.1056/NEJMoa022457

Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. / O'Brien, Stephen G.; Guilhot, François; Larson, Richard A.; Gathmann, Insa; Baccarani, Michele; Cervantes, Francisco; Cornelissen, Jan J.; Fischer, Thomas; Hochhaus, Andreas; Hughes, Timothy; Lechner, Klaus; Nielsen, Johan L.; Rousselot, Philippe; Reiffers, Josy; Saglio, Giuseppe; Shepherd, John; Simonsson, Bengt; Gratwohl, Alois; Goldman, John M.; Kantarjian, Hagop; Taylor, Kerry; Verhoef, Gregor; Bolton, Ann E.; Capdeville, Renaud; Druker, Brian J.

In: New England Journal of Medicine, Vol. 348, No. 11, 13.03.2003, p. 994-1004.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia

AU - O'Brien, Stephen G.

AU - Guilhot, François

AU - Larson, Richard A.

AU - Gathmann, Insa

AU - Baccarani, Michele

AU - Cervantes, Francisco

AU - Cornelissen, Jan J.

AU - Fischer, Thomas

AU - Hochhaus, Andreas

AU - Hughes, Timothy

AU - Lechner, Klaus

AU - Nielsen, Johan L.

AU - Rousselot, Philippe

AU - Reiffers, Josy

AU - Saglio, Giuseppe

AU - Shepherd, John

AU - Simonsson, Bengt

AU - Gratwohl, Alois

AU - Goldman, John M.

AU - Kantarjian, Hagop

AU - Taylor, Kerry

AU - Verhoef, Gregor

AU - Bolton, Ann E.

AU - Capdeville, Renaud

AU - Druker, Brian J.

PY - 2003/3/13

Y1 - 2003/3/13

N2 - BACKGROUND: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. METHODS: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. RESULTS After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy. CONCLUSIONS: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.

AB - BACKGROUND: Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML. METHODS: We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression. RESULTS After a median follow-up of 19 months, the estimated rate of a major cytogenetic response (0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome) at 18 months was 87.1 percent (95 percent confidence interval, 84.1 to 90.0) in the imatinib group and 34.7 percent (95 percent confidence interval, 29.3 to 40.0) in the group given interferon alfa plus cytarabine (P<0.001). The estimated rates of complete cytogenetic response were 76.2 percent (95 percent confidence interval, 72.5 to 79.9) and 14.5 percent (95 percent confidence interval, 10.5 to 18.5), respectively (P<0.001). At 18 months, the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group (P<0.001). Imatinib was better tolerated than combination therapy. CONCLUSIONS: In terms of hematologic and cytogenetic responses, tolerability, and the likelihood of progression to accelerated-phase or blast-crisis CML, imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML.

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U2 - 10.1056/NEJMoa022457

DO - 10.1056/NEJMoa022457

M3 - Article

VL - 348

SP - 994

EP - 1004

JO - New England Journal of Medicine

T2 - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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