TY  - JOUR
A1  - Proetel, Ulrike
A1  - Pletsch, Nadine
A1  - Lauseker, Michael
A1  - Müller, Martin C.
A1  - Hanfstein, Benjamin
A1  - Krause, Stefan W.
A1  - Kalmanti, Lida
A1  - Schreiber, Annette
A1  - Heim, Dominik
A1  - Baerlocher, Gabriela M.
A1  - Hofmann, Wolf-Karsten
A1  - Lange, Elisabeth
A1  - Einsele, Hermann
A1  - Wernli, Martin
A1  - Kremers, Stephan
A1  - Schlag, Rudolf
A1  - Müller, Lothar
A1  - Hänel, Mathias
A1  - Link, Hartmut
A1  - Hertenstein, Bernd
A1  - Pfirrmann, Markus
A1  - Hochhaus, Andreas
A1  - Hasford, Joerg
A1  - Hehlmann, Rüdiger
A1  - Saußele, Susanne
T1  - Older patients with chronic myeloid leukemia (≥65 years) profit more from higher imatinib doses than younger patients: a subanalysis of the randomized CML-Study IV
JF  - Annals of Hematology
N2  - The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to imatinib 400 mg/day (IM400) or imatinib 800 mg/day (IM800) and stratified according to age (≥65 years vs. <65 years) were compared regarding dose, response, adverse events, rates of progression, and survival. The full 800 mg dose was given after a 6-week run-in period with imatinib 400 mg/day. The dose could then be reduced according to tolerability. A total of 828 patients were randomized to IM400 or IM800. Seven hundred eighty-four patients were evaluable (IM400, 382; IM800, 402). One hundred ten patients (29 %) on IM400 and 83 (21 %) on IM800 were ≥65 years. The median dose per day was lower for patients ≥65 years on IM800, with the highest median dose in the first year (466 mg/day for patients ≥65 years vs. 630 mg/day for patients <65 years). Older patients on IM800 achieved major molecular remission and deep molecular remission as fast as younger patients, in contrast to standard dose imatinib with which older patients achieved remissions much later than younger patients. Grades 3 and 4 adverse events were similar in both age groups. Five-year relative survival for older patients was comparable to that of younger patients. We suggest that the optimal dose for older patients is higher than 400 mg/day. ClinicalTrials.gov identifier: NCT00055874
KW  - chronic myeloid leukemia
KW  - older patients
KW  - different imatinib dose regimens
KW  - early applied higher imatinib dosages
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121574
SN  - 0939-5555
VL  - 93
IS  - 7
ER  - 
TY  - JOUR
A1  - Saussele, Susanne
A1  - Hehlmann, Ruediger
A1  - Fabarius, Alice
A1  - Jeromin, Sabine
A1  - Proetel, Ulrike
A1  - Rinaldetti, Sebastien
A1  - Kohlbrenner, Katharina
A1  - Einsele, Hermann
A1  - Falge, Christine
A1  - Kanz, Lothar
A1  - Neubauer, Andreas
A1  - Kneba, Michael
A1  - Stegelmann, Frank
A1  - Pfreundschuh, Michael
A1  - Waller, Cornelius F.
A1  - Oppliger Leibundgut, Elisabeth
A1  - Heim, Dominik
A1  - Krause, Stefan W.
A1  - Hofmann, Wolf-Karsten
A1  - Hasford, Joerg
A1  - Pfirrmann, Markus
A1  - Müller, Martin C.
A1  - Hochhaus, Andreas
A1  - Lauseker, Michael
T1  - Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV
JF  - Leukemia
N2  - Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.
KW  - Chronic myeloid leukaemia
KW  - Molecularly targeted therapy
KW  - Risk factors
KW  - Risk factors
KW  - Translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227528
VL  - 32
IS  - 5
ER  -