Front-line treatment of Philadelphia positive chronic myeloid leukemia with imatinib and interferon-α: 5-year outcome

This study confirms the excellent response to imatinib front-line therapy in patients with chronic myeloid leukemia. By contrast, most patients discontinued pegylated interferon-α due to its side effects. In 2004, we reported the short-term results of a multicentric, phase 2 study of imatinib 400 mg daily and pegylated interferon-α in the treatment of 76 early chronic phase Philadelphia-positive chronic myeloid leukemia patients. In this report, we update the results with an observation time of five years. After two years of treatment, all but 10 patients (13%) had discontinued pegylated interferon-α. The complete cytogenetic response rate at five years was 87%, and 94% of complete cytogenetic responders maintained the complete cytogenetic response after five years. All but one complete cytogenetic response also achieved a major molecular response. These data confirm the excellent response to imatinib front-line and the stability of the complete cytogenetic response. Any possible additional benefit of the combination with interferon-α remains uncertain, due to low patient compliance.

[1]  M. Baccarani,et al.  Monitoring BCR-ABL transcript levels by real-time quantitative polymerase chain reaction: a linear regression equation to convert from BCR-ABL/B2M ratio to estimated BCR-ABL/ABL ratio. , 2007, Haematologica.

[2]  Francisco Cervantes,et al.  Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. , 2006, The New England journal of medicine.

[3]  C. Preudhomme,et al.  First Overall Molecular Response of the Randomized French SPIRIT Study on Behalf the Fi-LMC Group. , 2006 .

[4]  Francisco Cervantes,et al.  Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. , 2006, Blood.

[5]  Simona Soverini,et al.  Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. , 2006, Blood.

[6]  J. Hasford,et al.  Concept and feasibility of the randomized comparison of imatinib with imatinib combination therapies for chronic myeloid leukemia: The German CML Study IV - Pilot Phase , 2005 .

[7]  M. Baccarani,et al.  Imatinib and pegylated human recombinant interferon-alpha2b in early chronic-phase chronic myeloid leukemia. , 2004, Blood.

[8]  C. Sawyers,et al.  Four Years of Follow-Up of 1027 Patients with Late Chronic Phase (L-CP), Accelerated Phase (AP), or Blast Crisis (BC) Chronic Myeloid Leukemia (CML) Treated with Imatinib in Three Large Phase II Trials. , 2004 .

[9]  H. Kantarjian,et al.  Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-α , 2004 .

[10]  H. Kantarjian,et al.  High-dose imatinib mesylate therapy in newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia. , 2004, Blood.

[11]  H. Cavé,et al.  Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program , 2003, Leukemia.

[12]  Susan Branford,et al.  Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. , 2003, The New England journal of medicine.

[13]  Francisco Cervantes,et al.  Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. , 2003, The New England journal of medicine.

[14]  J. Issa,et al.  Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[15]  H. Kantarjian,et al.  Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. , 2002, Blood.

[16]  R. Larson,et al.  Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. , 2002, Blood.

[17]  M. Baccarani,et al.  Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. , 2002, Blood.

[18]  B. Druker,et al.  STI571: an inhibitor of the BCR-ABL tyrosine kinase for the treatment of chronic myelogenous leukaemia. , 2000, The Lancet. Oncology.

[19]  R. Hehlmann [Interferon-alpha in chronic myeloid leukemia]. , 1997, Fortschritte der Medizin.

[20]  Jürg Zimmermann,et al.  Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells , 1996, Nature Medicine.

[21]  G. Canellos,et al.  Chronic granulocytic leukemia. , 1976, The Medical clinics of North America.

[22]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[23]  H. Kantarjian,et al.  Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. , 2004, Blood.

[24]  H. Kantarjian,et al.  Imatinib mesylate therapy in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia: high incidence of early complete and major cytogenetic responses. , 2003, Blood.

[25]  M. Baccarani,et al.  Prognostic discrimination in "good-risk" chronic granulocytic leukemia. , 1984, Blood.