Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils
<b>Background</b> Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that FcγRI/CD64 overexpression in neutrophils of newly diagnosed MM patients is associated to inferior outcomes, reduced oxidative bursts...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/10/1455 |
| _version_ | 1797515190589194240 |
|---|---|
| author | Alessandra Romano Nunziatina Laura Parrinello Marina Parisi Vittorio Del Fabro Angelo Curtopelle Salvatore Leotta Concetta Conticello Francesco Di Raimondo |
| author_facet | Alessandra Romano Nunziatina Laura Parrinello Marina Parisi Vittorio Del Fabro Angelo Curtopelle Salvatore Leotta Concetta Conticello Francesco Di Raimondo |
| author_sort | Alessandra Romano |
| collection | DOAJ |
| description | <b>Background</b> Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that FcγRI/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. <b>Patients and methods</b> 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/μL. Neutrophil function was investigated by flow cytometry, including the phagocytosis, oxidative bursts, and median fluorescence intensity of FcγRI-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. <b>Results</b> Compared to controls, RRMM neutrophils had higher expression of FcγRI/CD64 and lower phagocytic activity and oxidative bursts. We maintained median leukocyte counts higher than 3.5 × 10<sup>9</sup>/L for 6 cycles, and median neutrophil counts higher than 1.5 × 10<sup>9</sup>/L, with only 6 (11%) patients developing grade 3–4 infections, without pomalidomide dose reduction. After 4 cycles of PomDex, FcγRI/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 FcγRI/CD64 expression, improving phagocytic activity and oxidative bursta as tested in vitro. <b>Conclusions</b> 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 FcγRI/CD64 overexpression. |
| first_indexed | 2024-03-10T06:42:01Z |
| format | Article |
| id | doaj.art-034633ba481e4014ac8e1efeb3939623 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T06:42:01Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-034633ba481e4014ac8e1efeb39396232023-11-22T17:32:09ZengMDPI AGBiomedicines2227-90592021-10-01910145510.3390/biomedicines9101455Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma NeutrophilsAlessandra Romano0Nunziatina Laura Parrinello1Marina Parisi2Vittorio Del Fabro3Angelo Curtopelle4Salvatore Leotta5Concetta Conticello6Francesco Di Raimondo7Dipartimento di Chirurgia e Specialità Medico-Chirurgiche, Università degli Studi di Catania, 95123 Catania, ItalyDivision of Hematology, AOU “Policlinico—Vittorio Emanuele”, 95123 Catania, ItalyDivision of Hematology, AOU “Policlinico—Vittorio Emanuele”, 95123 Catania, ItalyDivision of Hematology, AOU “Policlinico—Vittorio Emanuele”, 95123 Catania, ItalyDivision of Hematology, AOU “Policlinico—Vittorio Emanuele”, 95123 Catania, ItalyDivision of Hematology, AOU “Policlinico—Vittorio Emanuele”, 95123 Catania, ItalyDivision of Hematology, AOU “Policlinico—Vittorio Emanuele”, 95123 Catania, ItalyDipartimento di Chirurgia e Specialità Medico-Chirurgiche, Università degli Studi di Catania, 95123 Catania, Italy<b>Background</b> Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that FcγRI/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. <b>Patients and methods</b> 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/μL. Neutrophil function was investigated by flow cytometry, including the phagocytosis, oxidative bursts, and median fluorescence intensity of FcγRI-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. <b>Results</b> Compared to controls, RRMM neutrophils had higher expression of FcγRI/CD64 and lower phagocytic activity and oxidative bursts. We maintained median leukocyte counts higher than 3.5 × 10<sup>9</sup>/L for 6 cycles, and median neutrophil counts higher than 1.5 × 10<sup>9</sup>/L, with only 6 (11%) patients developing grade 3–4 infections, without pomalidomide dose reduction. After 4 cycles of PomDex, FcγRI/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 FcγRI/CD64 expression, improving phagocytic activity and oxidative bursta as tested in vitro. <b>Conclusions</b> 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 FcγRI/CD64 overexpression.https://www.mdpi.com/2227-9059/9/10/1455multiple myelomaneutrophilphagocytosisCD64 |
| spellingShingle | Alessandra Romano Nunziatina Laura Parrinello Marina Parisi Vittorio Del Fabro Angelo Curtopelle Salvatore Leotta Concetta Conticello Francesco Di Raimondo Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils Biomedicines multiple myeloma neutrophil phagocytosis CD64 |
| title | Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils |
| title_full | Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils |
| title_fullStr | Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils |
| title_full_unstemmed | Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils |
| title_short | Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils |
| title_sort | lenalidomide and pomalidomide improve function and induce fcγri cd64 in multiple myeloma neutrophils |
| topic | multiple myeloma neutrophil phagocytosis CD64 |
| url | https://www.mdpi.com/2227-9059/9/10/1455 |
| work_keys_str_mv | AT alessandraromano lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT nunziatinalauraparrinello lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT marinaparisi lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT vittoriodelfabro lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT angelocurtopelle lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT salvatoreleotta lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT concettaconticello lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils AT francescodiraimondo lenalidomideandpomalidomideimprovefunctionandinducefcgricd64inmultiplemyelomaneutrophils |