{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:20:37Z","timestamp":1762420837408,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 Politecnica delle Marche, Ancona, Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Early relapse in multiple myeloma (MM) is a major predictor of poor prognosis, regardless of cytogenetic risk or treatment intensity. Methods: Here we analyzed 1026 MM patients treated across 12 Italian hematology centers. FHR was defined as progression-free survival (PFS) \u226418 months in transplant-eligible (TE) and \u226412 months in non-transplant-eligible (NTE) patients. Logistic regression and ROC analysis were used to identify significant predictors of FHR and build a risk score. Results: FHR status was identified in 175 patients (17%). These patients had significantly shorter PFS (7 vs. 57.5 months) and overall survival (19 months vs. not reached; p &lt; 0.001). FHR status was associated with higher median LDH, lower Hb level, higher creatinine level and lower platelets count. Modified EASIX formula was built by these significant continuous variables, to be tested in a logistic analysis: [(LDH \u00d7 creatinine)\/(Hb \u00d7 PLT) \u00d7 100]. A significantly higher rate of FHR was found with a score &gt; 2.0 (89% vs. 11%, p &lt; 0.001). Multivariate logistic analysis selected the above formula, ECOG PS \u2265 2 and ISS III as factors associated with FHR. Scoring these variables according to OR, three groups of patients were segregated with a rate of FHR patients of 7%, 29.5%, and 63.5%, respectively. Treatment with anti-CD38 monoclonal antibodies was associated with lower FHR frequency. Conclusions: This study proposes a simple, clinically applicable model to identify FHR MM patients early in their disease course. However, very in-depth biological tools, not available in clinical practice, are needed to identify singularly risk of becoming FHR.<\/jats:p>","DOI":"10.3390\/cancers17213580","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:02:03Z","timestamp":1762419723000},"page":"3580","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Strange Case of Functional High-Risk Multiple Myeloma Patients: Is It Possible to Identify Them in Clinical Practice?"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4398-7860","authenticated-orcid":false,"given":"Sonia","family":"Mor\u00e8","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Dipartimento Scienze Cliniche e Molecolari (DISCLIMO), Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"},{"name":"Hematology Clinic, AOU delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2749-7347","authenticated-orcid":false,"given":"Massimo","family":"Offidani","sequence":"additional","affiliation":[{"name":"Hematology Clinic, AOU delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Corvatta","sequence":"additional","affiliation":[{"name":"Internal Medicine, Ospedale E. Profili, 60044 Fabriano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Za","sequence":"additional","affiliation":[{"name":"Hematology Clinic, Policlinico Agostino Gemelli, 00136 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4187-8912","authenticated-orcid":false,"given":"Francesca","family":"Fazio","sequence":"additional","affiliation":[{"name":"Hematology Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Gherardini","sequence":"additional","affiliation":[{"name":"Hematology Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-6485","authenticated-orcid":false,"given":"Velia","family":"Bongarzoni","sequence":"additional","affiliation":[{"name":"Department of Hematology, San Giovanni-Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Anaclerico","sequence":"additional","affiliation":[{"name":"Department of Hematology, San Giovanni-Addolorata Hospital, 00184 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Lymphoproliferative Diseases Unit, Tor Vergata University Hospital, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Hematology Department, Ospedale Sant\u2019Eugenio, 00144 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Cupelli","sequence":"additional","affiliation":[{"name":"Hematology Department, Ospedale Sant\u2019Eugenio, 00144 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-9343","authenticated-orcid":false,"given":"Carmine","family":"Liberatore","sequence":"additional","affiliation":[{"name":"Hematology Unit, Pescara Hospital, 65124 Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Padua","sequence":"additional","affiliation":[{"name":"UOC di Ematologia, Trapianto di Cellule Staminali e Terapia Genica, 03100 Frosinone, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Rago","sequence":"additional","affiliation":[{"name":"UOSD Ematologia ASL Roma1, 00193 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Gentili","sequence":"additional","affiliation":[{"name":"UOSD Ematologia Civitanova Marche AST Macerata, 62012 Civitanova Marche, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Latagliata","sequence":"additional","affiliation":[{"name":"UOC Hematology, Santa Rosa Hospital, 01100 Viterbo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariagrazia","family":"Garzia","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hematology San Camillo Forlanini Hospital, 00152 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iole","family":"Cordone","sequence":"additional","affiliation":[{"name":"IRCCS Istituto Nazionale Tumori Regina Elena Dipartimento di Ricerca, Diagnostica Avanzata ed Innovazione Tecnologica-IFO, 00144 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9116-503X","authenticated-orcid":false,"given":"Valeria","family":"Mezzanotte","sequence":"additional","affiliation":[{"name":"Lymphoproliferative Diseases Unit, Tor Vergata University Hospital, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Rossi","sequence":"additional","affiliation":[{"name":"Hematology Clinic, Policlinico Agostino Gemelli, 00136 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Di Landro","sequence":"additional","affiliation":[{"name":"Hematology Clinic, Policlinico Agostino Gemelli, 00136 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Zaira","family":"Limongi","sequence":"additional","affiliation":[{"name":"Hematology Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika","family":"Morsia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Dipartimento Scienze Cliniche e Molecolari (DISCLIMO), Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"},{"name":"Hematology Clinic, AOU delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4221-4125","authenticated-orcid":false,"given":"Antonella","family":"Poloni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences, Dipartimento Scienze Cliniche e Molecolari (DISCLIMO), Universit\u00e0 Politecnica delle Marche, 60121 Ancona, Italy"},{"name":"Hematology Clinic, AOU delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0688-4882","authenticated-orcid":false,"given":"Maria Teresa","family":"Petrucci","sequence":"additional","affiliation":[{"name":"Hematology Department of Translational and Precision Medicine, Azienda Policlinico Umberto I, Sapienza University of Rome, 00161 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U","article-title":"A clinical staging system for multiple myeloma","volume":"36","author":"Durie","year":"1975","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1200\/JCO.2005.04.242","article-title":"International staging system for multiple myeloma","volume":"23","author":"Greipp","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1200\/JCO.2015.61.2267","article-title":"Revised International Staging System for Multiple Myeloma","volume":"33","author":"Palumbo","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1200\/JCO.21.02614","article-title":"Second revision of the International Staging System (R2-ISS) for overall survival in multiple myeloma: A European Myeloma Network (EMN) report within the HARMONY project","volume":"40","author":"Cairns","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1200\/JCO-24-01893","article-title":"International Myeloma Society\/International Myeloma Working Group consensus recommendations on the definition of high-risk multiple myeloma","volume":"43","author":"Davies","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ho, M., Paruzzo, L., Minehart, J., Nabar, N., Noll, J.H., Luo, T., Chen, Y., Wang, Z., Patel, K., and Singh, A. (2025). Extramedullary multiple myeloma: Challenges and opportunities. Curr. Oncol., 32.","DOI":"10.3390\/curroncol32030182"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41408-024-01190-9","article-title":"Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma","volume":"14","author":"Nardi","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1200\/JCO.22.01226","article-title":"More than 2% of circulating tumor plasma cells defines plasma cell leukemia-like multiple myeloma","volume":"41","author":"Jelinek","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1182\/blood.2025029234","article-title":"Ultrasensitive detection of circulating multiple myeloma cells by next-generation flow after immunomagnetic enrichment","volume":"146","author":"Lasa","year":"2025","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bertamini, L., Fokkema, C., Rodriguez-Otero, P., van Duin, M., Terpos, E., Sonneveld, P., Mateos, M.V., Moreau, P., Usmani, S.Z., and Kumar, S.K. (2025). Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone. Blood, 8.","DOI":"10.1182\/blood.2025030113"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1182\/hematology.2023000443","article-title":"A rational approach to functional high-risk myeloma","volume":"2023","author":"Gay","year":"2023","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Banerjee, R., Cicero, K.I., Lee, S.S., Cowan, A.J., Zhang, Y., Patel, P., Thomas, A., Nguyen, T., Li, M., and Chen, H. (2023). Definers and drivers of functional high-risk multiple myeloma: Insight from genomic, transcriptomic, and immune profiling. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1240966"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Song, G.Y., Jung, S.H., Kim, K., Lee, J.H., Park, H., Choi, Y., Lim, H.S., Kim, W.S., Cho, H.J., and Yoon, D.H. (2020). Endothelial activation and stress index (EASIX) is a reliable predictor for overall survival in patients with multiple myeloma. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07317-y"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e433520","DOI":"10.1200\/EDBK_433520","article-title":"Navigating high-risk and ultra-high-risk multiple myeloma: Challenges and emerging strategies","volume":"44","author":"Rees","year":"2024","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/leu.2017.331","article-title":"Early relapse after autologous hematopoietic cell transplantation remains a poor prognostic factor in multiple myeloma but outcomes have improved over time","volume":"32","author":"Kumar","year":"2018","journal-title":"Leukemia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.3324\/haematol.2019.236588","article-title":"Early relapse after autologous transplant for myeloma is associated with poor survival regardless of cytogenetic risk","volume":"105","author":"Corre","year":"2020","journal-title":"Haematologica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/bjh.16793","article-title":"Early relapse after high-dose melphalan autologous stem cell transplant predicts inferior survival and is associated with high disease burden and genetically high-risk disease in multiple myeloma","volume":"193","author":"Bygrave","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1182\/blood-2019-129431","article-title":"Real world outcome for newly diagnosed patients with functional high-risk myeloma\u2014A Myeloma and Related Diseases Registry analysis","volume":"134","author":"Spencer","year":"2019","journal-title":"Blood"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1158\/1078-0432.CCR-20-0951","article-title":"Early relapse risk in patients with newly diagnosed multiple myeloma characterized by next-generation sequencing","volume":"26","author":"Zaccaria","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1038\/s41375-018-0057-5","article-title":"Early relapsed disease of multiple myeloma following up-front HDM-ASCT: A study based on the Danish Multiple Myeloma Registry in the period 2005 to 2014","volume":"32","author":"Sorrig","year":"2018","journal-title":"Leukemia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1038\/leu.2016.147","article-title":"Early relapse following initial therapy for multiple myeloma predicts poor outcomes in the era of novel agents","volume":"30","author":"Majithia","year":"2016","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/bmt.2008.180","article-title":"Impact of early relapse after auto-SCT for multiple myeloma","volume":"42","author":"Kumar","year":"2008","journal-title":"Bone Marrow Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"594","DOI":"10.3109\/10428194.2014.911863","article-title":"A gene expression based predictor for high-risk myeloma treated with intensive therapy and autologous stem cell rescue","volume":"56","author":"Wu","year":"2015","journal-title":"Leuk. Lymphoma"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.clml.2019.10.014","article-title":"Early relapse after autologous transplant is associated with very poor survival and identifies an ultra-high-risk group of patients with myeloma","volume":"20","author":"Kastritis","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1016\/j.clml.2017.10.009","article-title":"Early relapse for multiple myeloma patients undergoing single autologous stem cell therapy: A single-center experience","volume":"18","author":"Lee","year":"2018","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/bmt.2014.237","article-title":"Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents","volume":"50","author":"Reece","year":"2015","journal-title":"Bone Marrow Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1038\/bmt.2016.43","article-title":"Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: Analysis of the Singapore Multiple Myeloma Working Group","volume":"51","author":"Ong","year":"2016","journal-title":"Bone Marrow Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.1158\/1078-0432.CCR-21-0134","article-title":"Developing and validating a simplified score to predict early relapse in newly diagnosed multiple myeloma (S-ERMM): Analysis from a pooled dataset of 2190 patients","volume":"27","author":"Zaccaria","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e70127","DOI":"10.1002\/hem3.70127","article-title":"High-risk features of early relapse in newly diagnosed multiple myeloma: The impact of cytogenetics and response to initial therapy","volume":"9","author":"Manubens","year":"2025","journal-title":"HemaSphere"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, Y., Kuang, L., Huang, B., Liu, J., Chen, M., Li, X., Zhang, Y., Wang, H., Zhou, Q., and Lin, J. (2025). Early identification of the non-transplanted functional high-risk multiple myeloma: Insights from a predictive nomogram. Biomedicines, 13.","DOI":"10.3390\/biomedicines13010145"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Mor\u00e8, S., Offidani, M., Corvatta, L., Aloisi, S., Za, T., Fazio, F., Gherardini, M., Bongarzoni, V., Anaclerico, B., and Franceschini, L. (Clin. Lymphoma Myeloma Leuk., 2025). Cytogenetic features and their implications in clinical practice: A real-world analysis of a large cohort of multiple myeloma patients, Clin. Lymphoma Myeloma Leuk., in press.","DOI":"10.1016\/j.clml.2025.09.001"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"931","DOI":"10.7326\/0003-4819-115-12-931","article-title":"High serum lactate dehydrogenase level as a marker for drug resistance and short survival in multiple myeloma","volume":"115","author":"Dimopoulos","year":"1991","journal-title":"Ann. Intern. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1600-0609.2010.01466.x","article-title":"High serum lactate dehydrogenase adds prognostic value to the International Myeloma Staging System even in the era of novel agents","volume":"85","author":"Terpos","year":"2010","journal-title":"Eur. J. Haematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8335","DOI":"10.3892\/mmr.2017.7637","article-title":"LDHA promotes tumor metastasis by facilitating epithelial\u2013mesenchymal transition in renal cell carcinoma","volume":"16","author":"Zhao","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.2174\/138161212799504902","article-title":"Multiple biological activities of lactic acid in cancer: Influences on tumor growth, angiogenesis and metastasis","volume":"18","author":"Dhup","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Espinoza-Zamora, R., Zapata-Canto, N.P., Aguilera-Urbina, L.D., Cruz-Velazquez, J., Reyes-Maldonado, E., and Vela-Ojeda, J. (2025). Increased LDH Remains a Crucial Prognostic Factor in Patients with Multiple Myeloma. Arch Med Res, 56.","DOI":"10.1016\/j.arcmed.2025.103239"},{"key":"ref_38","first-page":"25","article-title":"Renal insufficiency in multiple myeloma: A systematic review and meta-analysis of all randomized trials from 2005\u20132019","volume":"52","author":"Mohyuddin","year":"2021","journal-title":"Arch. Med. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e296","DOI":"10.1038\/bcj.2015.20","article-title":"Improvement in renal function and its impact on survival in patients with newly diagnosed multiple myeloma","volume":"5","author":"Gonsalves","year":"2015","journal-title":"Blood Cancer J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1038\/s41375-023-02105-6","article-title":"Predictors of early morbidity and mortality in newly diagnosed multiple myeloma: Data from five randomized, controlled, phase III trials in 3700 patients","volume":"38","author":"Mai","year":"2024","journal-title":"Leukemia"},{"key":"ref_41","first-page":"S149","article-title":"Association of thrombocytopenia with disease burden, high-risk cytogenetics, and survival in newly diagnosed multiple myeloma patients","volume":"22","author":"Charalampous","year":"2022","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_42","unstructured":"Zeng, X., Liu, Y., Zhang, Y., Wang, Y., Li, Y., Wang, Y., and Zhang, Y. (2024). Association between platelet count and in-hospital mortality in critically ill patients with multiple myeloma: A retrospective cohort study. PLoS ONE, 19."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1182\/blood-2011-04-347484","article-title":"Multiple myeloma\u2013related deregulation of bone marrow\u2013derived CD34\u207a hematopoietic stem and progenitor cells","volume":"120","author":"Bruns","year":"2012","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e92","DOI":"10.1016\/j.clml.2019.09.150","article-title":"The bone marrow microenvironment of multiple myeloma promotes myeloma-related anemia by suppressing the differentiation of hematopoietic stem cells","volume":"19","author":"Liu","year":"2019","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"107037","DOI":"10.1016\/j.leukres.2023.107037","article-title":"Evaluation of the Simplified Score to Predict Early Relapse in Multiple Myeloma (S-ERMM) in the MMRF CoMMpass study","volume":"126","author":"Slade","year":"2023","journal-title":"Leuk. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1111\/bjh.19303","article-title":"Subsequent therapy and outcomes in patients with newly diagnosed multiple myeloma experiencing disease progression after quadruplet combinations","volume":"204","author":"Ravi","year":"2024","journal-title":"Br. J. Haematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1200\/JCO.23.01696","article-title":"Isatuximab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed high-risk multiple myeloma: Results from the GMMG-CONCEPT trial","volume":"42","author":"Leypoldt","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1182\/blood.2023023597","article-title":"Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed multiple myeloma: Results of the IFM 2018-04 trial","volume":"143","author":"Touzeau","year":"2024","journal-title":"Blood"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3945","DOI":"10.1200\/JCO.22.02567","article-title":"Daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone as induction and extended consolidation improves outcome in ultra-high-risk multiple myeloma: Results from the OPTIMUM\/MUKnine trial","volume":"41","author":"Kaiser","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.1182\/bloodadvances.2020002827","article-title":"A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma","volume":"4","author":"Munshi","year":"2020","journal-title":"Blood Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e890","DOI":"10.1016\/S2352-3026(23)00236-3","article-title":"Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): Final report of the multicentre, single-arm, phase 2 trial","volume":"10","author":"Costa","year":"2023","journal-title":"Lancet Haematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1182\/blood.2024026230","article-title":"Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: Analysis of the MIDAS trial","volume":"146","author":"Perrot","year":"2025","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1056\/NEJMoa2312054","article-title":"Daratumumab, bortezomib, lenalidomide, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma","volume":"390","author":"Sonneveld","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1182\/blood-2023-178882","article-title":"The Phase 2 CARTITUDE-2 Trial: Updated Efficacy and Safety of Ciltacabtagene Autoleucel in Patients with Multiple Myeloma and 1-3 Prior Lines of Therapy (Cohort A) and with Early Relapse after First Line Treatment (Cohort B)","volume":"142","author":"Hillengass","year":"2023","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1182\/blood-2022-162469","article-title":"KarMMa-2 Cohort 2a: Efficacy and Safety of Idecabtagene Vicleucel in Clinical High-Risk Multiple Myeloma Patients with Early Relapse after Frontline Autologous Stem Cell Transplantation","volume":"140","author":"Usmani","year":"2022","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3580\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:16:21Z","timestamp":1762420581000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/21\/3580"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":55,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["cancers17213580"],"URL":"https:\/\/doi.org\/10.3390\/cancers17213580","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]}}}