Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort.

Brune, Magdalena M; Stüssi, Georg; Lundberg, Pontus; Vela, Visar; Heim, Dominik; Manz, Markus G; Haralambieva, Eugenia; Pabst, Thomas; Banz, Yara; Bargetzi, Mario; Grobholz, Rainer; Fehr, Martin; Cogliatti, Sergio; Ossenkoppele, Gert J; Löwenberg, Bob; Rudolf, Christina Biaggi; Li, Qiyu; Passweg, Jakob; Mazzuchelli, Luca; Medinger, Michael; ... (2021). Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort. Annals of hematology, 100(5), pp. 1169-1179. Springer-Verlag 10.1007/s00277-021-04467-2

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This translational study aimed at gaining insight into the effects of lenalidomide in acute myeloid leukemia (AML). Forty-one AML patients aged 66 or older of the Swiss cohort of the HOVON-103 AML/SAKK30/10 study were included. After randomization, they received standard induction chemotherapy with or without lenalidomide. Bone marrow biopsies at diagnosis and before the 2nd induction cycle were obtained to assess the therapeutic impact on leukemic blasts and microenvironment. Increased bone marrow angiogenesis, as assessed by microvessel density (MVD), was found at AML diagnosis and differed significantly between the WHO categories. Morphological analysis revealed a higher initial MVD in AML with myelodysplasia-related changes (AML-MRC) and a more substantial decrease of microvascularization after lenalidomide exposure. A slight increase of T-bet-positive TH1-equivalents was identifiable under lenalidomide. In the subgroup of patients with AML-MRC, the progression-free survival differed between the two treatment regimens, showing a potential but not significant benefit of lenalidomide. We found no correlation between the cereblon genotype (the target of lenalidomide) and treatment response or prognosis. In conclusion, addition of lenalidomide may be beneficial to elderly patients suffering from AML-MRC, where it leads to a reduction of microvascularization and, probably, to an intensified specific T cell-driven anti-leukemic response.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Pabst, Thomas Niklaus and Banz Wälti, Yara

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0939-5555

Publisher:

Springer-Verlag

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

27 Sep 2021 14:18

Last Modified:

27 Sep 2021 14:18

Publisher DOI:

10.1007/s00277-021-04467-2

PubMed ID:

33704530

Uncontrolled Keywords:

Acute myeloid leukemia Bone marrow microenvironment Cereblon Lenalidomide Microvessel density T cells

BORIS DOI:

10.48350/159234

URI:

https://boris.unibe.ch/id/eprint/159234

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