4.7 Article

Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils

期刊

BIOMEDICINES
卷 9, 期 10, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines9101455

关键词

multiple myeloma; neutrophil; phagocytosis; CD64

资金

  1. International Myeloma Foundation
  2. AIRC [IG2018-ID22131]
  3. Research Funding for University of Catania, Italy (Piano per la Ricerca 2016-2018, FIR 2018-2020-F.D.R., Piano per la Ricerca 2018-2020 PIACERI, Universita degli Studi di Catania)
  4. A.I.L. (Associazione Italiana contro le Leucemie) sezione di Catania
  5. FON.CA.NE.SA (Fondazione catanese per la cura delle malattie neoplastiche del sangue)

向作者/读者索取更多资源

The study investigated the functional activity of neutrophils in RRMM patients treated with pomalidomide and dexamethasone. The results showed compromised neutrophil function but maintained high blood cell counts. Pomalidomide and lenalidomide were found to modulate the functional activity of neutrophils, despite chronic activation due to Fc gamma RI/CD64 overexpression.
Background Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that Fc gamma RI/CD64 overexpression in neutrophils of newly diagnosed MM patients is associated to inferior outcomes, reduced oxidative bursts and phagocytosis, with an increased risk of bacterial infections. Pomalidomide is a novel immune-modulatory drug approved for relapsed/refractory patients (RRMM), with drug-related neutropenia as major limitation to treatment. Patients and methods Herein, we describe a prospective analysis of 51 consecutive RRMM patients treated with pomalidomide and dexamethasone (PomDex) from March 2015 through December 2016, associated with secondary prophylaxis with filgrastim (G-CSF) in case of neutrophil count < 1500 cells/mu L. Neutrophil function was investigated by flow cytometry, including the phagocytosis, oxidative bursts, and median fluorescence intensity of Fc gamma RI-CD64. Controls included a group of newly diagnosed symptomatic MM (NDMM), asymptomatic (smoldering myeloma, MGUS) and healthy subjects referred to our Center in the same time-frame. Results Compared to controls, RRMM neutrophils had higher expression of Fc gamma RI/CD64 and lower phagocytic activity and oxidative bursts. We maintained median leukocyte counts higher than 3.5 x 10(9)/L for 6 cycles, and median neutrophil counts higher than 1.5 x 10(9)/L, with only 6 (11%) patients developing grade 3-4 infections, without pomalidomide dose reduction. After 4 cycles of PomDex, Fc gamma RI/CD64 was further increased in neutrophils, and phagocytic activity and oxidative bursts recovered independently from filgrastim exposure and the quality of hematological responses. Similarly, in NDMM patients, lenalidomide but not bortezomib upregulated Fc gamma RI/CD64 expression, improving phagocytic activity and oxidative bursta as tested in vitro. Conclusions Our combined biological and clinical data provide new information on the ability of pomalidomide and lenalidomide to modulate the functional activity of neutrophils, despite their chronic activation due to Fc gamma RI/CD64 overexpression.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据