Peripheral blood monocyte count is a dynamic prognostic biomarker in multiple myeloma

Blood Advances - Tập 7 - Trang 482-490 - 2023
Camille V. Edwards1, Hamza Hassan1,2, Cenk Yildirim3, Grace Ferri4, Karina P. Verma4, Mara E. Murray Horwitz4, Nathanael R. Fillmore3,5, Nikhil C. Munshi2,5
1Section of Hematology/Oncology, Boston Medical Center, Boston, MA
2Hematology and Oncology Department, Veterans Administration Boston Healthcare System, West Roxbury, MA
3Cooperative Studies Program Informatics Center, Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA
4Section of General Internal Medicine, Department of Medicine, Boston Medical Center, Boston, MA
5Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Tóm tắt

Abstract With the growing knowledge of multiple myeloma (MM) pathobiology and the introduction of novel therapies, risk stratification continues to evolve. Myeloid-derived suppressor cells and tumor-associated macrophages, derived from peripheral blood monocytes, support malignant plasma cell proliferation in the bone marrow. Because peripheral blood absolute monocyte count (AMC) is thought to reflect the bone marrow microenvironment, we sought to evaluate the prognostic significance of AMC in MM. We retrospectively analyzed 10 822 patients newly diagnosed with MM between 2000 and 2019 at Veteran’s Administration hospitals. We obtained AMC closest to diagnosis and every 3 months thereafter up to 2.5 years. Patients were stratified into 4 groups: low, normal, elevated, and severely elevated AMC (<0.2, 0.2-<0.8, 0.8-<1.25, and ≥1.25 × 103/mm3, respectively). Abnormal AMC at diagnosis was observed in 25.3% of the patients and was associated with an inferior overall survival (OS). In patients with low, severely elevated, elevated, and normal AMC, respectively, median OS at diagnosis was 2.3, 2.7, 3.1, and 3.6 years (P < .001) and at 2.5 years was 2.0, 2.6, 3.4, and 3.9 years (P < .001). Patients with normal AMC at diagnosis who developed an abnormal AMC >1 year after diagnosis also had an inferior OS relative to patients who maintained a normal AMC. Abnormal AMC was also associated with inferior OS independent of validated prognostic markers, including the international staging system and lactate dehydrogenase. Our findings provide novel clues for future prospective studies on the functional role of monocytes in MM, which could be a readily available metric for risk stratification.

Tài liệu tham khảo

Siegel, 2012, Cancer statistics, 2012, CA Cancer J Clin, 62, 10, 10.3322/caac.20138 Nandakumar, 2019, Continued improvement in survival in multiple myeloma (MM) including high-risk patients, J Clin Oncol, 37, 8039, 10.1200/JCO.2019.37.15_suppl.8039 Rajkumar, 2014, International myeloma working group updated criteria for the diagnosis of multiple myeloma, Lancet Oncol, 15, e538, 10.1016/S1470-2045(14)70442-5 Palumbo, 2015, Revised international staging system for multiple myeloma: a report from International Myeloma Working Group, J Clin Oncol, 33, 2863, 10.1200/JCO.2015.61.2267 Kastritis, 2017, Evaluation of the revised international staging system in an independent cohort of unselected patients with multiple myeloma, Haematologica, 102, 593, 10.3324/haematol.2016.145078 Favaloro, 2014, Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma, Leuk Lymphoma, 55, 2893, 10.3109/10428194.2014.904511 Berardi, 2013, Multiple myeloma macrophages: pivotal players in the tumor microenvironment, J Oncol, 2013, 183602 Greipp, 2005, International staging system for multiple myeloma, J Clin Oncol, 23, 3412, 10.1200/JCO.2005.04.242 Dosani, 2017, Significance of the absolute lymphocyte/monocyte ratio as a prognostic immune biomarker in newly diagnosed multiple myeloma, Blood Cancer J, 7, e579, 10.1038/bcj.2017.60 Embaby, 2020, Initial absolute monocyte count as an immune biomarker for clinical response in acute myeloid leukemia with monocytic differentiation, J Egypt Natl Cancer Inst, 32, 1 Friedman, 2016, Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi-institutional study, Am J Hematol, 91, 687, 10.1002/ajh.24376 Kumagai, 2014, Prognostic impact of preoperative monocyte counts in patients with resected lung adenocarcinoma, Lung Cancer, 85, 457, 10.1016/j.lungcan.2014.06.015 Lee, 2020, PD-L1 expression in bone marrow plasma cells as a biomarker to predict multiple myeloma prognosis: developing a nomogram-based prognostic model, Sci Rep, 10, 1 Sponaas, 2015, The proportion of CD16(+)CD14(dim) monocytes increases with tumor cell load in bone marrow of patients with multiple myeloma, Immun Inflamm Dis, 3, 94, 10.1002/iid3.53 Wilcox, 2011, The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma, Leukemia, 25, 1502, 10.1038/leu.2011.112 Görgün, 2013, Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans, Blood, 121, 2975, 10.1182/blood-2012-08-448548 Kawano, 2015, Targeting the bone marrow microenvironment in multiple myeloma, Immunol Rev, 263, 160, 10.1111/imr.12233 Ribatti, 2014, Macrophages in multiple myeloma, Immunol Lett, 161, 241, 10.1016/j.imlet.2013.12.010 Zheng, 2009, Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug–induced apoptosis, Blood, 114, 3625, 10.1182/blood-2009-05-220285 Bruns, 2012, Multiple myeloma–related deregulation of bone marrow–derived CD34+ hematopoietic stem and progenitor cells, Blood, 120, 2620, 10.1182/blood-2011-04-347484