{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:24:04Z","timestamp":1761899044573,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["24534","2021\/2025"],"award-info":[{"award-number":["24534","2021\/2025"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Progetti di Rilevante Interesse Nazionale (PRIN) 2022","award":["2022ZKKWLW","20229JM25N"],"award-info":[{"award-number":["2022ZKKWLW","20229JM25N"]}]},{"name":"PRIN PNRR 2022","award":["P2022E2JSK"],"award-info":[{"award-number":["P2022E2JSK"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Thrombosis is a common complication in multiple myeloma (MM) patients treated with immunomodulatory drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide. When combined with anti-CD38 monoclonal antibodies, these agents are highly effective but may increase thrombotic events (TE), potentially delaying therapy. This exploratory, hypothesis-generating analysis, conducted within the MMVision mono-institutional prospective study, included 53 MM patients who initiated IMiD plus anti-CD38 therapy between May 2021 and December 2022 (median follow-up: 18 months). Treatment regimens comprised lenalidomide (n = 36) or thalidomide (n = 15) with daratumumab, and pomalidomide (n = 2) with isatuximab. Most patients (n = 38) received frontline therapy, and all were given thromboprophylaxis according to guidelines, mainly aspirin (73%). Five patients (9.4%) developed VTE after a median of 48 days, managed with short-term low-molecular-weight heparin (LMWH). Exploratory analysis of 27 clinical\/laboratory parameters suggested possible associations between VTE and low levels of beta-2 microglobulin, ferritin, intact\/free lambda light chains, and monocyte-to-lymphocyte ratio. Notably, four of the five VTEs occurred in patients without lytic bone disease, typically associated with bone-driven inflammation in MM. Although all patients received aspirin prophylaxis from treatment initiation, it remains unclear whether thrombosis would also have occurred among those with higher inflammatory burden. These preliminary observations may indicate that in patients with relatively lower inflammation, aspirin prophylaxis could be less effective, potentially favoring VTE onset. In two VTE cases, cytokine profiling showed decreased M-CSF, SCLF-\u03b2, and MIP-1\u03b1, with increased G-CSF, raising the hypothesis of distinct immune-inflammatory pathways contributing to TEs. Given the limited number of patients and thrombotic events, and the cytokine data available for only two VTE cases, these associations should be regarded as exploratory and interpreted with caution. Overall, these exploratory findings warrant validation in larger, independent cohorts and may help generate hypotheses on how inflammatory signatures influence thrombotic risk and prophylaxis efficacy in MM patients receiving IMiD\/anti-CD38-based regimens.<\/jats:p>","DOI":"10.3390\/biom15111533","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:29:42Z","timestamp":1761895782000},"page":"1533","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammatory Biomarkers for Thrombotic Risk Assessment in Multiple Myeloma Patients on IMiD\/aCD38-Based Regimens: Insights from a Prospective Observational Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1522-4504","authenticated-orcid":false,"given":"Cirino","family":"Botta","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2541-4619","authenticated-orcid":false,"given":"Anna Maria","family":"Corsale","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Cammarata","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiana","family":"Di Fazio","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2070-0652","authenticated-orcid":false,"given":"Emilia","family":"Gigliotta","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Rizzuto","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Ingrasc\u00ec","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-7537","authenticated-orcid":false,"given":"Maria","family":"Speciale","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Aquilina","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Biondo","sequence":"additional","affiliation":[{"name":"Department of General Surgery and Medical-Surgical Specialties, Hematology Section, University of Catania, Catania 95123, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariasanta","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Mattana","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Siragusa","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (ProMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/s41571-025-01041-x","article-title":"EHA-EMN Evidence-Based Guidelines for Diagnosis, Treatment and Follow-up of Patients with Multiple Myeloma","volume":"22","author":"Dimopoulos","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.3324\/haematol.2022.280893","article-title":"Thrombosis in Multiple Myeloma: Risk Stratification, Antithrombotic Prophylaxis, and Management of Acute Events. A Consensus-Based Position Paper from an Ad Hoc Expert Panel","volume":"107","author":"Larocca","year":"2022","journal-title":"Haematologica"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.2174\/187152511794182846","article-title":"Thromboembolism with Immunomodulatory Agents in the Treatment of Multiple Myeloma","volume":"9","author":"Singh","year":"2011","journal-title":"Cardiovasc. Hematol. Agents Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/ajh.26806","article-title":"Thrombosis in Multiple Myeloma: Risk Estimation by Induction Regimen and Association with Overall Survival","volume":"98","author":"Charalampous","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/s12185-023-03690-z","article-title":"Cancer-Associated Thrombosis in Hematologic Malignancies","volume":"119","author":"Fukatsu","year":"2024","journal-title":"Int. J. Hematol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.3324\/haematol.2023.284778","article-title":"Targeted Anti-Cancer Agents and Risk of Venous Thromboembolism","volume":"109","author":"Verso","year":"2024","journal-title":"Haematologica"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1111\/bjh.18432","article-title":"Daratumumab plus Lenalidomide, Bortezomib and Dexamethasone in Newly Diagnosed Multiple Myeloma: Analysis of Vascular Thrombotic Events in the GRIFFIN Study","volume":"199","author":"Sborov","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/hon.3041","article-title":"Network Meta-Analysis of Randomized Trials in Multiple Myeloma: Efficacy and Safety in Frontline Therapy for Patients Not Eligible for Transplant","volume":"40","author":"Botta","year":"2022","journal-title":"Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Fotiou, D., Gavriatopoulou, M., and Terpos, E. (2020). Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools. Cancers, 12.","DOI":"10.3390\/cancers12010191"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1055\/s-0034-1370793","article-title":"Venous Thromboembolism in Multiple Myeloma","volume":"40","author":"Stefano","year":"2014","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1200\/JCO.2009.22.8197","article-title":"Venous Thromboembolism in the Hematologic Malignancies","volume":"27","author":"Falanga","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1538-7836.2011.04215.x","article-title":"Rates of Venous Thromboembolism in Multiple Myeloma Patients Undergoing Immunomodulatory Therapy with Thalidomide or Lenalidomide: A Systematic Review and Meta-analysis","volume":"9","author":"Carrier","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.critrevonc.2018.02.003","article-title":"Incidence of Venous Thromboembolism and Use of Anticoagulation in Hematological Malignancies: Critical Review of the Literature","volume":"124","author":"Annibali","year":"2018","journal-title":"Crit. Rev. Oncol.\/Hematol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1007\/s12185-020-02954-2","article-title":"Risk of Thromboembolism in Patients with Multiple Myeloma Treated with Daratumumab: A Systemic Review and Meta-Analysis","volume":"112","author":"Wang","year":"2020","journal-title":"Int. J. Hematol."},{"key":"ref_15","first-page":"214","article-title":"Potential Mechanisms of Resistance to Current Anti-Thrombotic Strategies in Multiple Myeloma","volume":"5","author":"Comerford","year":"2022","journal-title":"Cancer Drug Resist."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Plano, F., Gigliotta, E., Corsale, A.M., Azgomi, M.S., Santonocito, C., Ingrasc\u00ec, M., Di Carlo, L., Augello, A.E., Speciale, M., and Vullo, C. (2023). Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108852"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e511","DOI":"10.1038\/bcj.2016.118","article-title":"A Gene Expression Inflammatory Signature Specifically Predicts Multiple Myeloma Evolution and Patients Survival","volume":"6","author":"Botta","year":"2016","journal-title":"Blood Cancer J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Susca, N., Borrelli, P., Botta, C., and Solimando, A.G. (2025). Prognostic Impact of the Immune Microenvironment in Multiple Myeloma: A Meta-Analysis of Current Studies. Haematologica, 999.","DOI":"10.3324\/haematol.2024.286264"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Palomo, M., Moreno-Casta\u00f1o, A.B., Salas, M.Q., Escribano-Serrat, S., Rovira, M., Guillen-Olmos, E., Fernandez, S., Ventosa-Capell, H., Youssef, L., and Crispi, F. (2023). Endothelial Activation and Damage as a Common Pathological Substrate in Different Pathologies and Cell Therapy Complications. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1285898"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gidaro, A., Manetti, R., Delitala, A.P., Soloski, M.J., Lambertenghi Deliliers, G., Castro, D., Soldini, D., and Castelli, R. (2022). Incidence of Venous Thromboembolism in Multiple Myeloma Patients across Different Regimens: Role of Procoagulant Microparticles and Cytokine Release. J. Clin. Med., 11.","DOI":"10.3390\/jcm11102720"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15330338221106563","DOI":"10.1177\/15330338221106563","article-title":"Isatuximab in the Treatment of Multiple Myeloma: A Review and Comparison With Daratumumab","volume":"21","author":"Shen","year":"2022","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2364","DOI":"10.1002\/cncr.32065","article-title":"Daratumumab in Multiple Myeloma","volume":"125","author":"Nooka","year":"2019","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1200\/JCO.2013.48.7934","article-title":"International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation","volume":"32","author":"Palumbo","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1182\/blood-2018-99-116300","article-title":"Predicting Risk of Venous Thromboembolism in Multiple Myeloma: The Impede VTE Score","volume":"132","author":"Sanfilippo","year":"2018","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"840","DOI":"10.6004\/jnccn.2018.7273","article-title":"Derivation and Validation of a Risk Assessment Model for Immunomodulatory Drug\u2013Associated Thrombosis Among Patients With Multiple Myeloma","volume":"17","author":"Li","year":"2019","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1182\/blood.2022015727","article-title":"Abnormal Metaphase Cytogenetics Predicts Venous Thromboembolism in Myeloma: Derivation and Validation of the PRISM Score","volume":"140","author":"Chakraborty","year":"2022","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Abdi, J., and Nasr, P. (2025). Abnormalities of Primary and Secondary Hemostasis in Multiple Myeloma: Insights from Studies on Thrombopoiesis, the Coagulation System, and the Bone Marrow Microenvironment. Front. Hematol., 4.","DOI":"10.3389\/frhem.2025.1435193"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Isozumi, Y., Arai, R., Fujimoto, K., and Koyama, T. (2013). Activation of Coagulation by Lenalidomide-Based Regimens for the Treatment of Multiple Myeloma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064369"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.thromres.2023.01.010","article-title":"Patients with Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance Have Variably Increased Thrombin Generation and Different Sensitivity to the Anticoagulant Effect of Activated Protein C","volume":"223","author":"Ghansah","year":"2023","journal-title":"Thromb. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Fotiou, D., Dimopoulos, M.A., and Kastritis, E. (2022). Approach to Contemporary Risk Assessment, Prevention and Management of Thrombotic Complications in Multiple Myeloma. Cancers, 14.","DOI":"10.3390\/cancers14246216"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.blre.2009.07.002","article-title":"Basic Mechanisms and Pathogenesis of Venous Thrombosis","volume":"23","author":"Esmon","year":"2009","journal-title":"Blood Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1002\/ajh.26590","article-title":"Multiple Myeloma: 2022 Update on Diagnosis, Risk Stratification, and Management","volume":"97","author":"Rajkumar","year":"2022","journal-title":"Am. J. Hematol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1533\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:41:16Z","timestamp":1761896476000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/11\/1533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,31]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["biom15111533"],"URL":"https:\/\/doi.org\/10.3390\/biom15111533","relation":{},"ISSN":["2218-273X"],"issn-type":[{"type":"electronic","value":"2218-273X"}],"subject":[],"published":{"date-parts":[[2025,10,31]]}}}