Imatinib dose reduction in major molecular response of chronic
myeloid leukemia: results from the German Chronic Myeloid
Leukemia-Study IV

J 2019

Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV

MICHEL, Christian, Andreas BURCHERT, Andreas HOCHHAUS, Susanne SAUSSELE, Andreas NEUBAUER et. al.

Základní údaje

Originální název

Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV

Autoři

MICHEL, Christian (276 Německo), Andreas BURCHERT (276 Německo), Andreas HOCHHAUS (276 Německo), Susanne SAUSSELE (276 Německo), Andreas NEUBAUER (276 Německo), Michael LAUSEKER (276 Německo), Stefan W. KRAUSE (276 Německo), Hans-Jochem KOLB (276 Německo), Dieter Kurt HOSSFELD (276 Německo), Christoph NERL (276 Německo), Gabriela M. BAERLOCHER (756 Švýcarsko), Dominik HEIM (756 Švýcarsko), Tim H. BRUMMENDORF (276 Německo), Alice FABARIUS (276 Německo), Claudia HAFERLACH (276 Německo), Brigitte SCHLEGELBERGER (276 Německo), Leopold BALLEISEN (276 Německo), Maria-Elisabeth GOEBELER (276 Německo), Mathias HANEL (276 Německo), Anthony HO (276 Německo), Jolanta DENGLER (276 Německo), Christiane FALGE (276 Německo), Robert MOHLE (276 Německo), Stephan KREMERS (276 Německo), Michael KNEBA (276 Německo), Frank STEGELMANN (276 Německo), Claus-Henning KOHNE (276 Německo), HW LINDEMANN, Hans-Walter WALLER (276 Německo), Karsten SPIEKERMANN (276 Německo), Wolfgang E. BERDEL (276 Německo), Lothar MULLER (276 Německo), Matthias EDINGER (276 Německo), Jiří MAYER (203 Česká republika, domácí), Dietrich W. BEELEN (276 Německo), Martin BENTZ (276 Německo), Hartmut LINK (276 Německo), Bernd HERTENSTEIN (276 Německo), Roland FUCHS (276 Německo), Martin WERNLI (276 Německo), Frank SCHLEGEL (276 Německo), Rudolf SCHLAG (276 Německo), Maike DE WIT (276 Německo), Lorenz TRUMPER (276 Německo), Holger HEBART (276 Německo), Markus HAHN (276 Německo), Joerg THOMALLA (276 Německo), Christof SCHEID (276 Německo), Philippe SCHAFHAUSEN (276 Německo), Walter VERBEEK (276 Německo), Michael J. ECKART (276 Německo), Winfried GASSMANN (276 Německo), Michael SCHENK (276 Německo), Peter BROSSART (276 Německo), Thomas WUNDISCH (276 Německo), Thomas GEER (276 Německo), Stephan BILDAT (276 Německo), Erhardt SCHAFER (276 Německo), Joerg HASFORD (276 Německo), Ruediger HEHLMANN (276 Německo) a Markus PFIRRMANN (276 Německo)

Vydání

Haematologica, PAVIA, FERRATA STORTI FOUNDATION, 2019, 0390-6078

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30205 Hematology

Stát vydavatele

Itálie

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 7.116

Kód RIV

RIV/00216224:14110/19:00113239

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.3324/haematol.2018.206797

UT WoS

000466305600030

Klíčová slova anglicky

CHRONIC MYELOGENOUS LEUKEMIA; TREATMENT-FREE REMISSION; QUALITY-OF-LIFE; CHRONIC-PHASE; RANDOMIZED CML; SURVIVAL; DASATINIB; NILOTINIB; THERAPY; 5-YEAR

Štítky

14110212, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 5. 5. 2020 09:10, Mgr. Tereza Miškechová

Anotace

V originále

Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients.

Citovat

MICHEL, Christian, Andreas BURCHERT, Andreas HOCHHAUS, Susanne SAUSSELE, Andreas NEUBAUER, Michael LAUSEKER, Stefan W. KRAUSE, Hans-Jochem KOLB, Dieter Kurt HOSSFELD, Christoph NERL, Gabriela M. BAERLOCHER, Dominik HEIM, Tim H. BRUMMENDORF, Alice FABARIUS, Claudia HAFERLACH, Brigitte SCHLEGELBERGER, Leopold BALLEISEN, Maria-Elisabeth GOEBELER, Mathias HANEL, Anthony HO, Jolanta DENGLER, Christiane FALGE, Robert MOHLE, Stephan KREMERS, Michael KNEBA, Frank STEGELMANN, Claus-Henning KOHNE, HW LINDEMANN, Hans-Walter WALLER, Karsten SPIEKERMANN, Wolfgang E. BERDEL, Lothar MULLER, Matthias EDINGER, Jiří MAYER, Dietrich W. BEELEN, Martin BENTZ, Hartmut LINK, Bernd HERTENSTEIN, Roland FUCHS, Martin WERNLI, Frank SCHLEGEL, Rudolf SCHLAG, Maike DE WIT, Lorenz TRUMPER, Holger HEBART, Markus HAHN, Joerg THOMALLA, Christof SCHEID, Philippe SCHAFHAUSEN, Walter VERBEEK, Michael J. ECKART, Winfried GASSMANN, Michael SCHENK, Peter BROSSART, Thomas WUNDISCH, Thomas GEER, Stephan BILDAT, Erhardt SCHAFER, Joerg HASFORD, Ruediger HEHLMANN a Markus PFIRRMANN. Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV. Haematologica. PAVIA: FERRATA STORTI FOUNDATION, 2019, roč. 104, č. 5, s. 955-962. ISSN 0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2018.206797.

@article{1635156,
   author = {Michel, Christian and Burchert, Andreas and Hochhaus, Andreas and Saussele, Susanne and Neubauer, Andreas and Lauseker, Michael and Krause, Stefan W. and Kolb, HansandJochem and Hossfeld, Dieter Kurt and Nerl, Christoph and Baerlocher, Gabriela M. and Heim, Dominik and Brummendorf, Tim H. and Fabarius, Alice and Haferlach, Claudia and Schlegelberger, Brigitte and Balleisen, Leopold and Goebeler, MariaandElisabeth and Hanel, Mathias and Ho, Anthony and Dengler, Jolanta and Falge, Christiane and Mohle, Robert and Kremers, Stephan and Kneba, Michael and Stegelmann, Frank and Kohne, ClausandHenning and Lindemann, HW and Waller, HansandWalter and Spiekermann, Karsten and Berdel, Wolfgang E. and Muller, Lothar and Edinger, Matthias and Mayer, Jiří and Beelen, Dietrich W. and Bentz, Martin and Link, Hartmut and Hertenstein, Bernd and Fuchs, Roland and Wernli, Martin and Schlegel, Frank and Schlag, Rudolf and de Wit, Maike and Trumper, Lorenz and Hebart, Holger and Hahn, Markus and Thomalla, Joerg and Scheid, Christof and Schafhausen, Philippe and Verbeek, Walter and Eckart, Michael J. and Gassmann, Winfried and Schenk, Michael and Brossart, Peter and Wundisch, Thomas and Geer, Thomas and Bildat, Stephan and Schafer, Erhardt and Hasford, Joerg and Hehlmann, Ruediger and Pfirrmann, Markus},
   article_location = {PAVIA},
   article_number = {5},
   doi = {http://dx.doi.org/10.3324/haematol.2018.206797},
   keywords = {CHRONIC MYELOGENOUS LEUKEMIA; TREATMENT-FREE REMISSION; QUALITY-OF-LIFE; CHRONIC-PHASE; RANDOMIZED CML; SURVIVAL; DASATINIB; NILOTINIB; THERAPY; 5-YEAR},
   language = {eng},
   issn = {0390-6078},
   journal = {Haematologica},
   title = {Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV},
   url = {http://dx.doi.org/10.3324/haematol.2018.206797},
   volume = {104},
   year = {2019}
}

TY  - JOUR
ID  - 1635156
AU  - Michel, Christian - Burchert, Andreas - Hochhaus, Andreas - Saussele, Susanne - Neubauer, Andreas - Lauseker, Michael - Krause, Stefan W. - Kolb, Hans-Jochem - Hossfeld, Dieter Kurt - Nerl, Christoph - Baerlocher, Gabriela M. - Heim, Dominik - Brummendorf, Tim H. - Fabarius, Alice - Haferlach, Claudia - Schlegelberger, Brigitte - Balleisen, Leopold - Goebeler, Maria-Elisabeth - Hanel, Mathias - Ho, Anthony - Dengler, Jolanta - Falge, Christiane - Mohle, Robert - Kremers, Stephan - Kneba, Michael - Stegelmann, Frank - Kohne, Claus-Henning - Lindemann, HW - Waller, Hans-Walter - Spiekermann, Karsten - Berdel, Wolfgang E. - Muller, Lothar - Edinger, Matthias - Mayer, Jiří - Beelen, Dietrich W. - Bentz, Martin - Link, Hartmut - Hertenstein, Bernd - Fuchs, Roland - Wernli, Martin - Schlegel, Frank - Schlag, Rudolf - de Wit, Maike - Trumper, Lorenz - Hebart, Holger - Hahn, Markus - Thomalla, Joerg - Scheid, Christof - Schafhausen, Philippe - Verbeek, Walter - Eckart, Michael J. - Gassmann, Winfried - Schenk, Michael - Brossart, Peter - Wundisch, Thomas - Geer, Thomas - Bildat, Stephan - Schafer, Erhardt - Hasford, Joerg - Hehlmann, Ruediger - Pfirrmann, Markus
PY  - 2019
TI  - Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV
JF  - Haematologica
VL  - 104
IS  - 5
SP  - 955-962
EP  - 955-962
PB  - FERRATA STORTI FOUNDATION
SN  - 03906078
KW  - CHRONIC MYELOGENOUS LEUKEMIA
KW  - TREATMENT-FREE REMISSION
KW  - QUALITY-OF-LIFE
KW  - CHRONIC-PHASE
KW  - RANDOMIZED CML
KW  - SURVIVAL
KW  - DASATINIB
KW  - NILOTINIB
KW  - THERAPY
KW  - 5-YEAR
UR  - http://dx.doi.org/10.3324/haematol.2018.206797
L2  - http://dx.doi.org/10.3324/haematol.2018.206797
N2  - Standard first-line therapy of chronic myeloid leukemia is treatment with imatinib. In the randomized German Chronic Myeloid Leukemia-Study IV, more potent BCR-ABL inhibition with 800 mg ('high-dose') imatinib accelerated achievement of a deep molecular remission. However, whether and when a de-escalation of the dose intensity under high-dose imatinib can be safely performed without increasing the risk of losing deep molecular response is unknown. To gain insights into this clinically relevant question, we analyzed the outcome of imatinib dose reductions from 800 mg to 400 mg daily in the Chronic Myeloid Leukemia-Study IV. Of the 422 patients that were randomized to the 800 mg arm, 68 reduced imatinib to 400 mg after they had achieved at least a stable major molecular response. Of these 68 patients, 61 (90%) maintained major molecular remission on imatinib at 400 mg. Five of the seven patients who lost major molecular remission on the imatinib standard dose regained major molecular remission while still on 400 mg imatinib. Only two of 68 patients had to switch to more potent kinase inhibition to regain major molecular remission. Importantly, the lengths of the intervals between imatinib high-dose treatment before and after achieving major molecular remission were associated with the probabilities of maintaining major molecular remission with the standard dose of imatinib. Taken together, the data support the view that a deep molecular remission achieved with high-dose imatinib can be safely maintained with standard dose in most patients.
ER  -

MICHEL, Christian, Andreas BURCHERT, Andreas HOCHHAUS, Susanne SAUSSELE, Andreas NEUBAUER, Michael LAUSEKER, Stefan W. KRAUSE, Hans-Jochem KOLB, Dieter Kurt HOSSFELD, Christoph NERL, Gabriela M. BAERLOCHER, Dominik HEIM, Tim H. BRUMMENDORF, Alice FABARIUS, Claudia HAFERLACH, Brigitte SCHLEGELBERGER, Leopold BALLEISEN, Maria-Elisabeth GOEBELER, Mathias HANEL, Anthony HO, Jolanta DENGLER, Christiane FALGE, Robert MOHLE, Stephan KREMERS, Michael KNEBA, Frank STEGELMANN, Claus-Henning KOHNE, HW LINDEMANN, Hans-Walter WALLER, Karsten SPIEKERMANN, Wolfgang E. BERDEL, Lothar MULLER, Matthias EDINGER, Jiří MAYER, Dietrich W. BEELEN, Martin BENTZ, Hartmut LINK, Bernd HERTENSTEIN, Roland FUCHS, Martin WERNLI, Frank SCHLEGEL, Rudolf SCHLAG, Maike DE WIT, Lorenz TRUMPER, Holger HEBART, Markus HAHN, Joerg THOMALLA, Christof SCHEID, Philippe SCHAFHAUSEN, Walter VERBEEK, Michael J. ECKART, Winfried GASSMANN, Michael SCHENK, Peter BROSSART, Thomas WUNDISCH, Thomas GEER, Stephan BILDAT, Erhardt SCHAFER, Joerg HASFORD, Ruediger HEHLMANN a Markus PFIRRMANN. Imatinib dose reduction in major molecular response of chronic myeloid leukemia: results from the German Chronic Myeloid Leukemia-Study IV. \textit{Haematologica}. PAVIA: FERRATA STORTI FOUNDATION, 2019, roč.~104, č.~5, s.~955-962. ISSN~0390-6078. Dostupné z: https://dx.doi.org/10.3324/haematol.2018.206797.

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