Kantonsspital St.Gallen
login

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

Magdalena M Brune, Georg Stüssi, Pontus Lundberg, Visar Vela, Dominik Heim, Markus G Manz, Eugenia Haralambieva, Thomas Pabst, Yara Banz, Mario Bargetzi, Rainer Grobholz, Martin Fehr, Sergio B. Cogliatti, Gert J Ossenkoppele, Bob Löwenberg, Christina Biaggi Rudolf, Qiyu Li, Jakob Passweg, Luca Mazzuchelli, Michael Medinger, Alexandar Tzankov & Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) And Swiss Group For Clinical Cancer Research (SAKK)

abstract 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.
   
citation Brune M M, Stüssi G, Lundberg P, Vela V, Heim D, Manz M G, Haralambieva E, Pabst T, Banz Y, Bargetzi M, Grobholz R, Fehr M, Cogliatti S B, Ossenkoppele G J, Löwenberg B, Rudolf C B, Li Q, Passweg J, Mazzuchelli L, Medinger M, Tzankov A, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) And Swiss Group For Clinical Cancer Research (SAKK) . Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort. Ann Hematol 2021; 100:1169-1179.
   
type journal paper/review (English)
date of publishing 02-03-2021
journal title Ann Hematol (100/5)
ISSN electronic 1432-0584
pages 1169-1179
PubMed 33704530
DOI 10.1007/s00277-021-04467-2