Comprehensive analysis of clinical outcomes, infectious complications and microbiological data in newly diagnosed multiple myeloma patients: a retrospective observational study of 92 subjects.
Anti-CD38 antibody therapy
Listeria monocytogenes
Multiple myeloma
Sepsis
Septic shock
Journal
Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405
Informations de publication
Date de publication:
27 Jun 2024
27 Jun 2024
Historique:
received:
13
03
2024
accepted:
19
06
2024
medline:
28
6
2024
pubmed:
28
6
2024
entrez:
27
6
2024
Statut:
epublish
Résumé
Patients with multiple myeloma (MM) have an increased risk of sepsis due to underlying disease- and treatment-related immunosuppression. However, data on sepsis incidence, causative pathogens, and impact on outcomes in newly diagnosed MM (NDMM) are limited. We conducted a retrospective observational study of 92 NDMM patients who developed sepsis between 2022 and 2023 at a tertiary care center in Italy. Patient characteristics, sepsis criteria [Quick Sequential Organ Failure Assessment, Systemic Inflammatory Response Syndrome (SIRS)], microbiology results, and associations with progression-free survival (PFS) were analyzed. In this cohort of 92 critically-ill patients, pathogenic organisms were identified via microbiological culture in 74 cases. However, among the remaining 18 culture-negative patients, 9 exhibited a SIRS score of 2 and another 9 had a SIRS score of 4, suggestive of a clinical presentation consistent with sepsis despite negative cultures. Common comorbidities included renal failure (60%), anemia (71%), and bone disease (83%). Gram-negative (28%) and Gram-positive (23%) bacteria were frequent causative organisms, along with fungi (20%). Cox Univariate analyses for PFS showed statically significant HR in patients with albumin ≥ 3.5 vs < 3.5 (HR = 5.04, p < 0.001), Karnofsky performance status ≥ 80 vs < 80 (HR = 2.01, p = 0.002), and early-stage vs late-stage disease by International Staging System (HR = 4.76 and HR = 12.52, both p < 0.001) and Revised International Staging System (R-ISS III vs R-ISS I, HR = 7.38, p < 0.001). Sepsis is common in NDMM and associated with poor outcomes. Risk stratification incorporating sepsis severity, comorbidities, and disease stage may help guide preventive strategies and optimize MM management.
Identifiants
pubmed: 38937383
doi: 10.1007/s10238-024-01411-2
pii: 10.1007/s10238-024-01411-2
doi:
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
137Subventions
Organisme : Fondo per il Programma Nazionale di Ricerca e Progetti di Rilevante Interesse Nazionale - PRIN
ID : 2022ZKKWLW
Informations de copyright
© 2024. The Author(s).
Références
Mateos MV, San Miguel JF. Management of multiple myeloma in the newly diagnosed patient. Hematol Am Soc Hematol Educ Program. 2017;2017(1):498–507.
doi: 10.1182/asheducation-2017.1.498
de la Rubia J, Cejalvo MJ, Ribas P. Infectious complications in patients with newly diagnosed multiple myeloma: a complication from the past? Leuk Lymphoma. 2016;57(2):258–68.
doi: 10.3109/10428194.2015.1088647
pubmed: 26428053
Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011;364(11):1046–60.
doi: 10.1056/NEJMra1011442
pubmed: 21410373
Russell BM, Avigan DE. Immune dysregulation in multiple myeloma: the current and future role of cell-based immunotherapy. Int J Hematol. 2023;117(5):652–9.
doi: 10.1007/s12185-023-03579-x
pubmed: 36964840
pmcid: 10039687
Sørrig R, Klausen TW, Salomo M, Vangsted A, Gimsing P. Risk factors for infections in newly diagnosed Multiple Myeloma patients: a Danish retrospective nationwide cohort study. Eur J Haematol. 2019;102(2):182–90.
doi: 10.1111/ejh.13190
pubmed: 30485563
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.
doi: 10.1001/jama.2016.0287
pubmed: 26903338
pmcid: 4968574
Chicca IJ, Heaney JL, Iqbal G, et al. Stratifying risk of infection and response to therapy in patients with myeloma: a prognostic study. NIHR J Libr. 2020. https://doi.org/10.3310/eme07100 .
doi: 10.3310/eme07100
Lin C, Shen H, Zhou S, et al. Assessment of infection in newly diagnosed multiple myeloma patients: risk factors and main characteristics. BMC Infect Dis. 2020;20(1):699.
doi: 10.1186/s12879-020-05412-w
pubmed: 32972385
pmcid: 7517606
Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and management of multiple myeloma: a review. JAMA. 2022;327(5):464–77.
doi: 10.1001/jama.2022.0003
pubmed: 35103762
Khan S, Vaisman A, Hota SS, et al. Listeria susceptibility in patients with multiple myeloma receiving daratumumab-based therapy. JAMA Oncol. 2020;6(2):293–4.
doi: 10.1001/jamaoncol.2019.5098
pubmed: 31774462
Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on sepsis-related problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–10.
doi: 10.1007/BF01709751
pubmed: 8844239
Simpson SQ. SIRS in the time of sepsis-3. Chest. 2018;153(1):34–8.
doi: 10.1016/j.chest.2017.10.006
pubmed: 29037526
Kumar SK, Rajkumar V, Kyle RA, et al. Multiple myeloma. Nat Rev Dis Primer. 2017;3:17046.
doi: 10.1038/nrdp.2017.46
Teh BW, Harrison SJ, Slavin MA, Worth LJ. Epidemiology of bloodstream infections in patients with myeloma receiving current era therapy. Eur J Haematol. 2017;98(2):149–53.
doi: 10.1111/ejh.12813
pubmed: 27717026
Offidani M, Corvatta L, Morè S, et al. Daratumumab for the management of newly diagnosed and relapsed/refractory multiple myeloma: current and emerging treatments. Front Oncol. 2020;10: 624661.
doi: 10.3389/fonc.2020.624661
pubmed: 33680948
Raje NS, Anaissie E, Kumar SK, et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 2022;9(2):e143–61.
doi: 10.1016/S2352-3026(21)00283-0
pubmed: 35114152
Lim C, Sinha P, Harrison SJ, Quach H, Slavin MA, Teh BW. Epidemiology and risks of infections in patients with multiple myeloma managed with new generation therapies. Clin Lymphoma Myeloma Leuk. 2021;21(7):444-450.e3.
doi: 10.1016/j.clml.2021.02.002
pubmed: 33722538
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International myeloma working group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-548.
doi: 10.1016/S1470-2045(14)70442-5
pubmed: 25439696
Davies F, Rifkin R, Costello C, et al. Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US. Ann Hematol. 2021;100(9):2325–37.
doi: 10.1007/s00277-021-04534-8
pubmed: 33970288
pmcid: 8357697
Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals Oncol. 2017;28:iv52–61. https://doi.org/10.1093/annonc/mdx096 .
doi: 10.1093/annonc/mdx096
Geng C, Yang G, Wang H, et al. Deep and partial immunoparesis is a poor prognostic factor for newly diagnosed multiple myeloma patients. Leuk Lymphoma. 2021;62(4):883–90.
doi: 10.1080/10428194.2020.1855345
pubmed: 33275060
Teh BW, Teng JC, Urbancic K, et al. Invasive fungal infections in patients with multiple myeloma: a multi-center study in the era of novel myeloma therapies. Haematologica. 2015;100(1):e28-31.
doi: 10.3324/haematol.2014.114025
pubmed: 25304609
pmcid: 4281332
Vacca A, Melaccio A, Sportelli A, et al. Subcutaneous immunoglobulins in patients with multiple myeloma and secondary hypogammaglobulinemia: a randomized trial. Clin Immunol. 2018;191:110–5.
doi: 10.1016/j.clim.2017.11.014
pubmed: 29191714
PDTA per l’Identificazione Precoce e la Gestione Tempestiva della Sepsi nel paziente adulto. In: https://www.sanita.puglia.it/documents/36067/434549/delibera+1158-2020+All.1.pdf/47b2f3bf-42fd-407c-a5f6-997fabf411ae . Accessed 20 December 2023.
Evans L, Rhodes A, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med. 2021;49(11):e1063–143. https://doi.org/10.1097/CCM.0000000000005337 .
doi: 10.1097/CCM.0000000000005337
pubmed: 34605781
Piedra-Quintero ZL, Wilson Z, Nava P, Guerau-de-Arellano M. CD38: an immunomodulatory molecule in inflammation and autoimmunity. Front Immunol. 2020. https://doi.org/10.3389/fimmu.2020.597959 .
doi: 10.3389/fimmu.2020.597959
pubmed: 33329591
pmcid: 7734206
Lischke T, Heesch K, Schumacher V, Schneider M, Haag F, Koch-Nolte F, Mittrücker HW. CD38 controls the innate immune response against listeria monocytogenes. Infect Immun. 2013;81(11):4091–9. https://doi.org/10.1128/IAI.00340-13 .
doi: 10.1128/IAI.00340-13
pubmed: 23980105
pmcid: 3811837
Partida-Sánchez S, Randall TD, Lund FE. Innate immunity is regulated by CD38, an ecto-enzyme with ADP-ribosyl cyclase activity. Microbes Infect. 2003;5(1):49–58. https://doi.org/10.1016/S1286-4579(02)00055-2 .
doi: 10.1016/S1286-4579(02)00055-2
pubmed: 12593973
Cook G, Pawlyn C, Cairns DA, Jackson GH. Defining FiTNEss for treatment for multiple myeloma. Lancet Healthy Longev. 2022;3(11):e729–30. https://doi.org/10.1016/S2666-7568(22)00218-5 .
doi: 10.1016/S2666-7568(22)00218-5
pubmed: 36356621
Sørrig R, Klausen TW, Salomo M, et al. Immunoparesis in newly diagnosed Multiple Myeloma patients: effects on overall survival and progression free survival in the Danish population. PLoS ONE. 2017;12(12):e0188988. https://doi.org/10.1371/journal.pone.0188988 .
doi: 10.1371/journal.pone.0188988
pubmed: 29216227
pmcid: 5720701