Peripheral blood cytogenetics allows treatment monitoring and early identification of treatment failure to lenalidomide in MDS patients: results of the LE-MON-5 trial.

Abstract

Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome, <5% bone marrow (BM) blasts and isolated 5q-deletion received lenalidomide within the German MDS study group phase-II clinical trial LE-MON-5 (EudraCT:2008-001866-10) of the University of Duesseldorf, Germany. Cytogenetic monitoring was performed by chromosome banding analyses (CBA) of BM cells and fluorescence in situ hybridization (FISH) analyses of peripheral blood (PB) mononuclear CD34+ cells using extended probe panels. Out of 144 patients screened for study enrollment, 24% failed to meet inclusion criteria due to cytogenetic findings. Eighty-seven patients were followed with a median observation time of 30 months. Cytogenetic response detected by FISH and CBA in 74 and 66% of patients, respectively, was predictive for hematologic response as well as of high prognostic relevance. After 2 years, AML rate was 8% for all patients. Karyotype evolution was detected in 21 (FISH)-34% (CBA) of patients associated with significantly shorter AML-free survival. Disease progression was first detectable on the cytogenetic level on average 5-6 months before recurrence of transfusion dependence. Our data show for the first time in a prospective setting that a cytogenetic monitoring from the PB helps to early identify treatment failure and progressive disease in lenalidomide-treated patients to improve clinical management.

TRIAL REGISTRATION:

EudraCT:2008-001866-10.

• Authors: Friederike Braulke, Xenia Schulz, Ulrich Germing, Esther Schuler, Uwe Platzbecker, Florian Nolte, Wolf-Karsten Hofmann, Aristoteles Giagounidis, Katharina Götze, Michael Lübbert, Richard F Schlenk, Julie Schanz, Ulrike Bacher, Arnold Ganser, Guntram Büsche, Anne Letsch, Philippe Schafhausen, Gesine Bug, Tim H Brümmendorf, Rainer Haas, Lorenz Trümper, Katayoon Shirneshan, Detlef Haase
• Journal: Annals of hematology (Ann Hematol) Vol. 96 Issue 6 Pg. 887-894 (Jun 2017) ISSN: 1432-0584 [Electronic] Germany
• PMID: 28374162 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Angiogenesis Inhibitors
• Antigens, CD34
• Thalidomide
• Lenalidomide

Topics

• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (therapeutic use)
• Antigens, CD34 (blood)
• Chromosome Banding
• Chromosome Deletion
• Chromosomes, Human, Pair 5 (genetics)
• Disease-Free Survival
• Female
• Germany
• Humans
• In Situ Hybridization, Fluorescence
• Karyotyping
• Lenalidomide
• Leukemia, Myeloid (diagnosis, genetics)
• Leukocytes, Mononuclear (metabolism)
• Male
• Middle Aged
• Myelodysplastic Syndromes (drug therapy, genetics)
• Prognosis
• Thalidomide (analogs & derivatives, therapeutic use)
• Treatment Failure