Randomized Controlled Trial

. 2017 Mar 9;376(10):917-927.

doi: 10.1056/NEJMoa1609324.

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia

Andreas Hochhaus¹, Richard A Larson¹, François Guilhot¹, Jerald P Radich¹, Susan Branford¹, Timothy P Hughes¹, Michele Baccarani¹, Michael W Deininger¹, Francisco Cervantes¹, Satoko Fujihara¹, Christine-Elke Ortmann¹, Hans D Menssen¹, Hagop Kantarjian¹, Stephen G O'Brien¹, Brian J Druker¹; IRIS Investigators

Collaborators, Affiliations

Collaborators

IRIS Investigators:
S Durrant, A Schwarer, D Joske, J Seymour, A Grigg, D Ma, C Arthur, K Bradstock, D Joshua, A Louwagie, P Martiat, N Straetmans, A Bosly, C Shustik, J Lipton, D Forrest, I Walker, D-C Roy, M Rubinger, I Bence-Bruckler, D Stewart, M Kovacs, A R Turner, H Birgens, O Bjerrum, T Facon, J-L Harousseau, M Tulliez, A Guerci, D Blaise, F Maloisel, M Michallet, D Hossfeld, R Mertelsmann, R Andreesen, C Nerl, M Freund, N Gattermann, K Hoeffken, G Ehninger, O Ottmann, C Peschel, S Frühauf, A Neubauer, P Le Coutre, W Aulitzky, R Fanin, G Rosti, F Mandelli, E Morra, A Carella, M Lazzarino, M Petrini, P Rossi Ferrini, F Nobile, V Liso, F Ferrara, V Rizzoli, G Fioritoni, G Martinelli, G Ossenkoppele, P Browett, T Gedde-Dahl, J-M Tangen, I Dahl, J Odriozola, J C Hernández Boluda, J L Steegmann, C Cañizo, A Sureda, J Diaz, A Granena, M N Fernández, L Stenke, C Paul, M Bjoreman, C Malm, H Wadenvik, P-G Nilsson, I Turesson, U Hess, M Solenthaler, J M Goldman, N Russel, G Mufti, J Cavenagh, R E Clark, A R Green, T L Holyoake, G S Lucas, G Smith, D W Milligan, S J Rule, A K Burnett, R Moroose, M Wetzler, J Bearden, R Brown, M Lobell, S Cataland, I Rabinowitz, B Meisenberg, J Gabrilove, K Thompson, S Graziano, P Emanuel, H Gross, P Cobb, R Bhatia, S Dakhil, D Irwin, B Issell, S Pavletic, P Kuebler, E Layhe, P Butera, J Glass, J Moore, B Grant, H Niell, R Herzig, H Burris, B Peterson, B Powell, M Kalaycio, D Stirewalt, W Samlowski, E Berman, S Limentani, T Seay, T Shea, L Akard, G Smith, P Becker, S DeVine, R Hart, R Veith, J Wade, M Brunvand, R Silver, L Kalman, D Strickland, M Shurafa, A Bashey, R Shadduck, S Cooper, H Safah, M Rubenstein, R Collins, A Keller, R Stone, M Tallman, D Stevens, A Pecora, M Agha, H Holmes, B J Druker, F Guilhot, R A Larson, S G O’Brien, J Rowe, C A Schiffer, M Buyse, M Baccarani, F Cervantes, J Cornelissen, T Fischer, A Hochhaus, T Hughes, H Kantarjian, K Lechner, J L Nielsen, J Reiffers, P Rousselot, G Saglio, J Shepherd, B Simonsson, A Gratwohl, K Taylor, G Verhoef

Affiliation

¹ From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).

PMID: 28273028
PMCID: PMC5901965
DOI: 10.1056/NEJMoa1609324

Randomized Controlled Trial

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia

Andreas Hochhaus et al. N Engl J Med. 2017.

. 2017 Mar 9;376(10):917-927.

doi: 10.1056/NEJMoa1609324.

Authors

Collaborators

IRIS Investigators:
S Durrant, A Schwarer, D Joske, J Seymour, A Grigg, D Ma, C Arthur, K Bradstock, D Joshua, A Louwagie, P Martiat, N Straetmans, A Bosly, C Shustik, J Lipton, D Forrest, I Walker, D-C Roy, M Rubinger, I Bence-Bruckler, D Stewart, M Kovacs, A R Turner, H Birgens, O Bjerrum, T Facon, J-L Harousseau, M Tulliez, A Guerci, D Blaise, F Maloisel, M Michallet, D Hossfeld, R Mertelsmann, R Andreesen, C Nerl, M Freund, N Gattermann, K Hoeffken, G Ehninger, O Ottmann, C Peschel, S Frühauf, A Neubauer, P Le Coutre, W Aulitzky, R Fanin, G Rosti, F Mandelli, E Morra, A Carella, M Lazzarino, M Petrini, P Rossi Ferrini, F Nobile, V Liso, F Ferrara, V Rizzoli, G Fioritoni, G Martinelli, G Ossenkoppele, P Browett, T Gedde-Dahl, J-M Tangen, I Dahl, J Odriozola, J C Hernández Boluda, J L Steegmann, C Cañizo, A Sureda, J Diaz, A Granena, M N Fernández, L Stenke, C Paul, M Bjoreman, C Malm, H Wadenvik, P-G Nilsson, I Turesson, U Hess, M Solenthaler, J M Goldman, N Russel, G Mufti, J Cavenagh, R E Clark, A R Green, T L Holyoake, G S Lucas, G Smith, D W Milligan, S J Rule, A K Burnett, R Moroose, M Wetzler, J Bearden, R Brown, M Lobell, S Cataland, I Rabinowitz, B Meisenberg, J Gabrilove, K Thompson, S Graziano, P Emanuel, H Gross, P Cobb, R Bhatia, S Dakhil, D Irwin, B Issell, S Pavletic, P Kuebler, E Layhe, P Butera, J Glass, J Moore, B Grant, H Niell, R Herzig, H Burris, B Peterson, B Powell, M Kalaycio, D Stirewalt, W Samlowski, E Berman, S Limentani, T Seay, T Shea, L Akard, G Smith, P Becker, S DeVine, R Hart, R Veith, J Wade, M Brunvand, R Silver, L Kalman, D Strickland, M Shurafa, A Bashey, R Shadduck, S Cooper, H Safah, M Rubenstein, R Collins, A Keller, R Stone, M Tallman, D Stevens, A Pecora, M Agha, H Holmes, B J Druker, F Guilhot, R A Larson, S G O’Brien, J Rowe, C A Schiffer, M Buyse, M Baccarani, F Cervantes, J Cornelissen, T Fischer, A Hochhaus, T Hughes, H Kantarjian, K Lechner, J L Nielsen, J Reiffers, P Rousselot, G Saglio, J Shepherd, B Simonsson, A Gratwohl, K Taylor, G Verhoef

Affiliation

¹ From Abteilung Hämatologie-Onkologie, Universitätsklinikum Jena, Jena, Germany (A.H.); the Department of Medicine, University of Chicago, Chicago (R.A.L.); INSERM Centre d'Investigation Clinique 1402, Centre Hospitalier Universitaire de Poitiers, Poitiers, France (F.G.); Fred Hutchinson Cancer Research Center, Seattle (J.P.R.); Centre for Cancer Biology, SA Pathology, University of South Australia and University of Adelaide (S.B.), and the South Australian Health and Medical Research Institute and University of Adelaide (T.P.H.), Adelaide, SA, Australia; University of Bologna, Bologna, Italy (M.B.); the University of Utah Huntsman Cancer Institute, Salt Lake City (M.W.D.); the Hematology Department, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (F.C.); Novartis, Basel, Switzerland (S.F., C.-E.O., H.D.M.); M.D. Anderson Cancer Center, Houston (H.K.); the University of Newcastle, Newcastle, United Kingdom (S.G.O.); and Knight Cancer Institute, Oregon Health and Science University and Howard Hughes Medical Institute, Portland (B.J.D.).

PMID: 28273028
PMCID: PMC5901965
DOI: 10.1056/NEJMoa1609324

Abstract

Background: Imatinib, a selective BCR-ABL1 kinase inhibitor, improved the prognosis for patients with chronic myeloid leukemia (CML). We conducted efficacy and safety analyses on the basis of more than 10 years of follow-up in patients with CML who were treated with imatinib as initial therapy.

Methods: In this open-label, multicenter trial with crossover design, we randomly assigned patients with newly diagnosed CML in the chronic phase to receive either imatinib or interferon alfa plus cytarabine. Long-term analyses included overall survival, response to treatment, and serious adverse events.

Results: The median follow-up was 10.9 years. Given the high rate of crossover among patients who had been randomly assigned to receive interferon alfa plus cytarabine (65.6%) and the short duration of therapy before crossover in these patients (median, 0.8 years), the current analyses focused on patients who had been randomly assigned to receive imatinib. Among the patients in the imatinib group, the estimated overall survival rate at 10 years was 83.3%. Approximately half the patients (48.3%) who had been randomly assigned to imatinib completed study treatment with imatinib, and 82.8% had a complete cytogenetic response. Serious adverse events that were considered by the investigators to be related to imatinib were uncommon and most frequently occurred during the first year of treatment.

Conclusions: Almost 11 years of follow-up showed that the efficacy of imatinib persisted over time and that long-term administration of imatinib was not associated with unacceptable cumulative or late toxic effects. (Funded by Novartis Pharmaceuticals; IRIS ClinicalTrials.gov numbers, NCT00006343 and NCT00333840 .).

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Conflict of interest statement

No other potential conflict of interest relevant to this article was reported.

Figures

**Figure 1**
Enrollment and Randomization of Patients and Censoring of Data for the Analysis of Overall Survival at 10 Years.

**Figure 2. Kaplan–Meier Estimated Overall Survival Rates at 10 Years in the Intention-to-Treat Population**
Shown is the overall survival over time among patients assigned to each trial group. For the curve for the group of patients who had been randomly assigned to receive interferon alfa plus cytarabine, data include survival among the 363 patients who crossed over to imatinib (65.6%). These patients crossed over to imatinib after a median of 0.8 years of receiving interferon alfa plus cytarabine. In patients with no reported death (whether because they were known to be alive or because their survival status was unknown), survival was censored (tick marks) at the date of last contact.

See this image and copyright information in PMC

Comment in

Imatinib Changed Everything.
Longo DL. Longo DL. N Engl J Med. 2017 Mar 9;376(10):982-983. doi: 10.1056/NEJMe1700833. N Engl J Med. 2017. PMID: 28273011 No abstract available.
[Treatment of chronic myeloid leukemia with imatinib : IRIS study].
Saußele S, Nitschmann S. Saußele S, et al. Internist (Berl). 2017 Nov;58(11):1220-1221. doi: 10.1007/s00108-017-0322-0. Internist (Berl). 2017. PMID: 28929180 German. No abstract available.

References

1. Rumpold H, Webersinke G. Molecular pathogenesis of Philadelphia-positive chronic myeloid leukemia — is it all BCR-ABL? Curr Cancer Drug Targets. 2011;11:3–19. - PubMed
1. Cohen MH, Williams G, Johnson JR, et al. Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res. 2002;8:935–42. - PubMed
1. O’Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003;348:994–1004. - PubMed
1. Druker BJ, Guilhot F, O’Brien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17. - PubMed
1. Hochhaus A, O’Brien SG, Guilhot F, et al. Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia. Leukemia. 2009;23:1054–61. - PubMed

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Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia

Collaborators

Affiliation

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia

Authors

Collaborators

Affiliation

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

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