Lenalidomide consolidation treatment in patients with multiple myeloma suppresses myelopoieses but spares erythropoiesis. Issue 10 (13th August 2016)

• Record Type: Journal Article
• Authors: Wilk, Christian Matthias; Heinzler, Niklas; Boquoi, Amelie; Cadeddu, Ron‐Patrick; Strapatsas, Tobias; Dienst, Ariane; Majidi, Fatemeh; Deenen, René; Bruns, Ingmar; Schroeder, Thomas; Köhrer, Karl; Haas, Rainer; Kobbe, Guido; Fenk, Roland
• Is Part Of: International journal of cancer. Volume 139:Issue 10(2016:Nov. 15)
• Page Start: 2343
• Page End: 2352
• Publication Date: 2016-08-13
• Subjects: multiple myeloma -- lenalidomide -- hematopoietic stem cells; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.30257
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : New drugs for the treatment of multiple myeloma (MM) comprise immunomodulatory substances such as lenalidomide and related compounds. While lenalidomide has found its way into first‐line treatment as well as into relapse therapy, little is known about lenalidomide effects on normal hematopoietic stem and progenitor cells (HSPCs). In this study, we investigated whether HSPCs are influenced by lenalidomide on a phenotypic, functional and gene expression level. For that purpose, samples from patients with MM were obtained who underwent equivalent first‐line treatment including induction therapy, cytotoxic stem cell mobilization and high‐dose melphalan therapy followed by autologous blood stem cell transplantation and a subsequent uniform lenalidomide consolidation treatment within a prospective clinical trial. We found that after six months of lenalidomide therapy, the number of CD34 + HSPCs decreased. Additionally, lenalidomide affects the numerical composition of hematopoietic cells in the bone marrow while it does not affect long‐term HSPC proliferation in vitro . We found a significant amplification of fetal hemoglobin (HbF) expression on a transcriptional level and can confirm a stimulated erythropoiesis on a phenotypic level. These effects were accompanied by silencing of the TGF‐β signaling pathway on the gene expression and protein level that is known to be amplified in active MM. However, these pleiotropic effects gave no evidence for mutagenic potential. In conclusion, lenalidomide does not exert long‐term effects on proliferation of HSPCs but instead promotes erythropoiesis by shifting hemoglobin expression toward HbF and by silencing the TGF‐β signaling pathway. Abstract : What's new? Drugs that modulate the immune system are often used to treat multiple myeloma. However, long‐term effects of these drugs on normal hematopoietic stem and progenitor cells (HSPCs) are uncertain. In this study, the authors analyzed HSPCs after six months of lenalidomide therapy. Gene expression in the TGF‐β pathway was reduced; there were also fewer granulocytes and CD34 + HSPCs, and more erythrocytes. However, proliferation of HSPCs was not affected, nor was there any gene expression signature predicting development of MDS/AML. Thus, lenalidomide is unlikely to cause long‐term functional impairment of these cells.