Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV

Saussele S, Hehlmann R, Fabarius A, Jeromin S, Proetel U, Rinaldetti S, Kohlbrenner K, Einsele H, Falge C, Kanz L, Neubauer A, Kneba M, Stegelmann F, Pfreundschuh M, Waller CF, Leibundgut EO, Heim D, Krause S, Hofmann WK, Hasford J, Pfirrmann M, Mueller MC, Hochhaus A, Lauseker M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Leukemia Springer Nature

Book Volume: 32

Pages Range: 1222-1228

Journal Issue: 5

DOI: 10.1038/s41375-018-0055-7

Abstract

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.

Authors with CRIS profile

Stefan Krause Department of Medicine 5 – Haematology and Oncology

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) MLL Münchner Leukämielabor GmbH DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Klinikum Nürnberg DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Philipps-Universität Marburg DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) Inselspital, Universitätsspital Bern CH Switzerland (CH) Universitätsspital Basel CH Switzerland (CH) Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Universitätsklinikum Jena DE Germany (DE)

How to cite

APA:

Saussele, S., Hehlmann, R., Fabarius, A., Jeromin, S., Proetel, U., Rinaldetti, S.,... Lauseker, M. (2018). Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV. Leukemia, 32(5), 1222-1228. https://dx.doi.org/10.1038/s41375-018-0055-7

MLA:

Saussele, Susanne, et al. "Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV." Leukemia 32.5 (2018): 1222-1228.

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