Integrative Multi-omics Analysis to Predict Monoclonal Gammopathies Clinical Evolution

NCT07214324 | Recruiting

• 1 other identifier: 849/2022/TESS/IRCCSRE
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

This prospective, multicenter, observational study aims to identify molecular and immunological markers associated with disease progression in patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). By integrating genomic, transcriptomic, immunophenotypic, and oral microbiome analyses, the study seeks to characterize the biological mechanisms underlying the transition to symptomatic multiple myeloma (MM). The study also includes in vitro modeling to investigate bone damage and immune dysfunction. Healthy volunteers (HV) undergoing joint replacement surgery for osteoarthritis will serve as controls. The ultimate goal is to improve early risk stratification and support future preventive strategies through a multi-omics approach. There is a pressing need for new strategies to identify high-risk individuals based on biological rather than purely clinical parameters. This study proposes an integrative, multi-omics approach to investigate the transition from MGUS/SMM to MM. By analyzing the immunome and oral microbiome alongside molecular profiling, the goal is to identify reliable biomarkers of progression. The resulting insights could be enable more accurate risk stratification and guide the design of future preventive clinical trials aimed at delaying or halting disease evolution.

Conditions

Monoclonal Gammopathy of Undetermined Significance (MGUS); Smoldering Multiple Myeloma (SMM); Multiple Myeloma (MM)

Keywords

plasma cells; multi-omics; biomarkers; bone marrow microenvironment; microbiome

Outcome Measures

Primary Outcomes (3)

• Bone marrow and peripheral blood immunophenotypic characterization

  Multiparametric flow cytometry of bone marrow CD138- cells and peripheral blood mononuclear cells (PBMCs) to define immune subsets and to assess alterations associated with monoclonal gammopathies progression.

  up to 24 months

• Genomic and transcriptomic profiling of plasma cell

  Next-generation sequencing (NGS) analysis of bone marrow CD138+ plasma cells, including targeted 14-gene mutation panels, copy number alterations by ultra-low-pass whole genome sequencing, RNA sequencing, and single-cell transcriptomics to identify molecular signatures of disease evolution.

  Up to 24 months

• Single-cell and spatial transcriptomic analyses

  Single-cell RNAseq, antibody-based sequencing (ABseq), TCR sequencing, and spatial transcriptomics on bone marrow biopsies to characterize clonal heterogeneity, cell-cell interactions, and microenvironmental influences during progression from MGUS/SMM to Multiple Myeloma.

  up to 24 months

Secondary Outcomes (2)

• Evaluation of oral microbiome composition

  up to 24, months

• Functional validation of genetic profiles in osteolytic disease

  24 months

Study Arms (2)

MGUS, SMM and MM patients

Patients with monoclonal gammopathy of undeterminated significance, smoldering multiple myeloma, or multiple myeloma

Other: Collection of biological material

Healthy volunteers

Patients with a clinical and radiological diagnosis of osteoarthritis who undergo endo or arthro-prosthesis surgery

Other: Collection of biological material

Interventions

Collection of biological material OTHER

For MGUS, SMM and MM patients, biological material (bone marrow aspirate, bone marrow biopsy, peripheral blood) consists exclusively of left-over samples obtained during routine diagnostic procedures and clinical practice management of their disease. For healthy volunteers, biological material includes waste bone tissue obtained during orthopedic surgery (endo- or arthro-prosthesis) and peripheral blood collected for research purposes. Both cohort of patient will be asked to donate gingival crevicular fluid (GCF) (this is a non-invasive procedure with no associated risks).

Healthy volunteers; MGUS, SMM and MM patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients with MGUS, SMM, or MM (with or without bone lytic lesions), as well as patient with osteoarthritis undergoing joint surgery (endoprosthesis or artroplasty) (Healty Volunteers)

You may qualify if:

• Age \>18 years
• Male or female patients
• Histologically confirmed diagnosis of MGUS, SMM, or MM according to ESMO 2021 guidelines
• Willing and able to provide written informed consent
• HEALTHY VOLUNTEERS (HV)
• Age \>60 years
• Diagnosis of osteoarthritis (OA)
• Scheduled for hospitalization for surgical treatment of OA (endoprosthesis or arthroplasty)
• Willing and able to provide written informed consent

You may not qualify if:

• Patients:
• Active current infection
• Autoimmune disease
• Women of childbearing potential unable to exclude pregnancy
• Use of high-dose corticosteroids within the past 7 days, potentially affecting immunome composition
• Healthy Volunteers:
• Prior joint surgery or severe joint deformity
• Recent trauma, osteonecrosis, or OA caused by prior/current joint infection
• Metabolic disorders
• Previous or current cancer diagnosis
• Autoimmune diseases (e.g., rheumatoid arthritis)

Sponsors & Collaborators

• Azienda USL Reggio Emilia - IRCCS: lead
• Ministero della Salute, Italy: collaborator
• European Union: collaborator

Study Sites (4)

Istituto Ortopedico Rizzoli IRCCS

Bologna, Italy

ACTIVE NOT RECRUITING

UO Ematologia Azienda Ospedaliero-Universitaria "Policlinico Rodolico San Marco"

Catania, Italy

ACTIVE NOT RECRUITING

UOC di Ematologia, Dipartimento di Oncologia, AOU Policlinico "Paolo Giaccone"

Palermo, Italy

ACTIVE NOT RECRUITING

S.C Ematologia - Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, Italy

RECRUITING

Related Publications (7)

• Rossi M, Altomare E, Botta C, Gallo Cantafio ME, Sarvide S, Caracciolo D, Riillo C, Gaspari M, Taverna D, Conforti F, Critelli P, Bertucci B, Iannone M, Polera N, Scumaci D, Arbitrio M, Amodio N, Di Martino MT, Paiva B, Tagliaferri P, Tassone P. miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma. Leukemia. 2021 Mar;35(3):823-834. doi: 10.1038/s41375-020-0947-1. Epub 2020 Jul 6.

  PMID: 32632096 BACKGROUND

• Leone P, Solimando AG, Malerba E, Fasano R, Buonavoglia A, Pappagallo F, De Re V, Argentiero A, Silvestris N, Vacca A, Racanelli V. Actors on the Scene: Immune Cells in the Myeloma Niche. Front Oncol. 2020 Oct 29;10:599098. doi: 10.3389/fonc.2020.599098. eCollection 2020.

  PMID: 33194767 BACKGROUND

• Bolli N, Maura F, Minvielle S, Gloznik D, Szalat R, Fullam A, Martincorena I, Dawson KJ, Samur MK, Zamora J, Tarpey P, Davies H, Fulciniti M, Shammas MA, Tai YT, Magrangeas F, Moreau P, Corradini P, Anderson K, Alexandrov L, Wedge DC, Avet-Loiseau H, Campbell P, Munshi N. Genomic patterns of progression in smoldering multiple myeloma. Nat Commun. 2018 Aug 22;9(1):3363. doi: 10.1038/s41467-018-05058-y.

  PMID: 30135448 BACKGROUND

• Ziccheddu B, Da Via MC, Lionetti M, Maeda A, Morlupi S, Dugo M, Todoerti K, Oliva S, D'Agostino M, Corradini P, Landgren O, Iorio F, Pettine L, Pompa A, Manzoni M, Baldini L, Neri A, Maura F, Bolli N. Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma. Clin Cancer Res. 2021 Dec 1;27(23):6479-6490. doi: 10.1158/1078-0432.CCR-20-4366. Epub 2021 Sep 15.

  PMID: 34526359 BACKGROUND

• Robiou du Pont S, Cleynen A, Fontan C, Attal M, Munshi N, Corre J, Avet-Loiseau H. Genomics of Multiple Myeloma. J Clin Oncol. 2017 Mar 20;35(9):963-967. doi: 10.1200/JCO.2016.70.6705. Epub 2017 Feb 13.

  PMID: 28297630 BACKGROUND

• Morgan GJ, Walker BA, Davies FE. The genetic architecture of multiple myeloma. Nat Rev Cancer. 2012 Apr 12;12(5):335-48. doi: 10.1038/nrc3257.

  PMID: 22495321 BACKGROUND

• Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011 Mar 17;364(11):1046-60. doi: 10.1056/NEJMra1011442. No abstract available.

  PMID: 21410373 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Malignant plasma cells were purified from bone marrow mononuclear cells, and genomic DNA was extracted for subsequent genomic analyses.

MeSH Terms

Conditions

Monoclonal Gammopathy of Undetermined Significance; Smoldering Multiple Myeloma; Multiple Myeloma

Condition Hierarchy (Ancestors)

Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases; Precancerous Conditions; Neoplasms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders

Study Officials

• Antonino Neri, MD, PhD

  Azienda USL - IRCCS di Reggio Emilia

  STUDY CHAIR

Central Study Contacts

Noemi Puccio

CONTACT

noemi.puccio@ausl.re.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 9, 2025
• Study Start: March 17, 2025
• Primary Completion: August 12, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 23, 2026

Record last verified: 2025-10

Locations

IT (4)