Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV
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Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV. / Hehlmann, Rüdiger; Müller, Martin C; Lauseker, Michael; Hanfstein, Benjamin; Fabarius, Alice; Schreiber, Annette; Proetel, Ulrike; Pletsch, Nadine; Pfirrmann, Markus; Haferlach, Claudia; Schnittger, Susanne; Einsele, Hermann; Dengler, Jolanta; Falge, Christiane; Kanz, Lothar; Neubauer, Andreas; Kneba, Michael; Stegelmann, Frank; Pfreundschuh, Michael; Waller, Cornelius F; Spiekermann, Karsten; Baerlocher, Gabriela M; Ehninger, Gerhard; Heim, Dominik; Heimpel, Hermann; Nerl, Christoph; Krause, Stefan W; Hossfeld, Dieter K; Kolb, Hans-Jochem; Hasford, Joerg; Saußele, Susanne; Hochhaus, Andreas.
in: J CLIN ONCOL, Jahrgang 32, Nr. 5, 2014, S. 415-23.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Deep molecular response is reached by the majority of patients treated with imatinib, predicts survival, and is achieved more quickly by optimized high-dose imatinib: results from the randomized CML-study IV
AU - Hehlmann, Rüdiger
AU - Müller, Martin C
AU - Lauseker, Michael
AU - Hanfstein, Benjamin
AU - Fabarius, Alice
AU - Schreiber, Annette
AU - Proetel, Ulrike
AU - Pletsch, Nadine
AU - Pfirrmann, Markus
AU - Haferlach, Claudia
AU - Schnittger, Susanne
AU - Einsele, Hermann
AU - Dengler, Jolanta
AU - Falge, Christiane
AU - Kanz, Lothar
AU - Neubauer, Andreas
AU - Kneba, Michael
AU - Stegelmann, Frank
AU - Pfreundschuh, Michael
AU - Waller, Cornelius F
AU - Spiekermann, Karsten
AU - Baerlocher, Gabriela M
AU - Ehninger, Gerhard
AU - Heim, Dominik
AU - Heimpel, Hermann
AU - Nerl, Christoph
AU - Krause, Stefan W
AU - Hossfeld, Dieter K
AU - Kolb, Hans-Jochem
AU - Hasford, Joerg
AU - Saußele, Susanne
AU - Hochhaus, Andreas
PY - 2014
Y1 - 2014
N2 - PURPOSE: Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival.PATIENTS AND METHODS: Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival.RESULTS: Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression.CONCLUSION: MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.
AB - PURPOSE: Deep molecular response (MR(4.5)) defines a subgroup of patients with chronic myeloid leukemia (CML) who may stay in unmaintained remission after treatment discontinuation. It is unclear how many patients achieve MR(4.5) under different treatment modalities and whether MR(4.5) predicts survival.PATIENTS AND METHODS: Patients from the randomized CML-Study IV were analyzed for confirmed MR(4.5) which was defined as ≥ 4.5 log reduction of BCR-ABL on the international scale (IS) and determined by reverse transcriptase polymerase chain reaction in two consecutive analyses. Landmark analyses were performed to assess the impact of MR(4.5) on survival.RESULTS: Of 1,551 randomly assigned patients, 1,524 were assessable. After a median observation time of 67.5 months, 5-year overall survival (OS) was 90%, 5-year progression-free-survival was 87.5%, and 8-year OS was 86%. The cumulative incidence of MR(4.5) after 9 years was 70% (median, 4.9 years); confirmed MR(4.5) was 54%. MR(4.5) was reached more quickly with optimized high-dose imatinib than with imatinib 400 mg/day (P = .016). Independent of treatment approach, confirmed MR(4.5) at 4 years predicted significantly higher survival probabilities than 0.1% to 1% IS, which corresponds to complete cytogenetic remission (8-year OS, 92% v 83%; P = .047). High-dose imatinib and early major molecular remission predicted MR(4.5). No patient with confirmed MR(4.5) has experienced progression.CONCLUSION: MR(4.5) is a new molecular predictor of long-term outcome, is reached by a majority of patients treated with imatinib, and is achieved more quickly with optimized high-dose imatinib, which may provide an improved therapeutic basis for treatment discontinuation in CML.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Benzamides
KW - Cytarabine
KW - Disease Progression
KW - Disease-Free Survival
KW - Female
KW - Fusion Proteins, bcr-abl
KW - Humans
KW - Interferon-alpha
KW - Leukemia, Myelogenous, Chronic, BCR-ABL Positive
KW - Male
KW - Middle Aged
KW - Molecular Targeted Therapy
KW - Piperazines
KW - Proportional Hazards Models
KW - Protein Kinase Inhibitors
KW - Pyrimidines
KW - Remission Induction
KW - Risk Factors
KW - Time Factors
KW - Treatment Outcome
KW - Young Adult
U2 - 10.1200/JCO.2013.49.9020
DO - 10.1200/JCO.2013.49.9020
M3 - SCORING: Journal article
C2 - 24297946
VL - 32
SP - 415
EP - 423
JO - J CLIN ONCOL
JF - J CLIN ONCOL
SN - 0732-183X
IS - 5
ER -