EHA-EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma

. 2025 Jul 07 ; () : . [epub] 20250707

Status Publisher Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid40624367
Odkazy

PubMed 40624367
DOI 10.1038/s41571-025-01041-x
PII: 10.1038/s41571-025-01041-x
Knihovny.cz E-zdroje

Since the publication in 2021 of the European Hematology Association (EHA) Clinical Practice Guidelines for the treatment of patients with smouldering multiple myeloma (SMM) and multiple myeloma (MM), developed in collaboration with the European Society for Medical Oncology, a novel international staging system (R2-ISS) has been developed, several prognostic factors are entering clinical practice (such as minimal residual disease, circulating plasma cells and monoclonal protein assessed by mass spectrometry) and, at the time of writing, 14 novel regimens have been approved by the EMA and/or the FDA for the treatment of patients with MM. A multidisciplinary group of experts from the EHA and European Myeloma Network, based in various institutions mostly located in Europe, have updated the previous guidelines and produced algorithms for everyday clinical practice that incorporate levels of evidence and grades of recommendation based on the aforementioned new data. In these Evidence-Based Guidelines, we provide key treatment recommendations for both patients with newly diagnosed MM and those with relapsed and/or refractory MM, including guidance for the use of established drugs as well as contemporary immunotherapies. Novel approaches for the management of patients with SMM focus on those who might require early intervention. Finally, we provide recommendations for myeloma-related complications and adverse events, such as bone disease, renal impairment and infections, as well as for those associated with T cell-mobilizing therapies, such as cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome.

Ankara Liv Hospital Istinye University Ankara Turkey

Australian Centre for Blood Diseases Monash University Melbourne Victoria Australia

Centre de Recherche Saint Antoine INSERM UMRs938 Sorbonne Université Paris France

Clinic of Hematology University Clinical Center of Serbia Medical Faculty University of Belgrade Belgrade Serbia

Clinica Universidad de Navarra CIMA IDISNA CIBERONC Pamplona Spain

Department of Biotechnology and Health Science University of Torino Turin Italy

Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Haematology The Royal Marsden Hospital London UK

Department of Hemato Oncology University Hospital Ostrava Ostrava Czech Republic

Department of Hematology Amsterdam UMC Vrije Universiteit Amsterdam Cancer Center Amsterdam Amsterdam Netherlands

Department of Hematology and Bone Marrow Transplantation Poznan University of Medical Sciences Poznań Poland

Department of Hematology and Oncology Interdisciplinary Cancer Center and Comprehensive Cancer Center Freiburg University of Freiburg Faculty of Freiburg Freiburg Germany

Department of Hematology Erasmus MC Cancer Institute Rotterdam Netherlands

Department of Hematology Lille University Hospital Lille France

Department of Hematology University Hospital Hôtel Dieu Nantes France

Department of Hematology University Hospital Leuven Leuven Belgium

Department of Internal Medicine 2 University Hospital Wurzburg Wurzburg Germany

Department of Malignant Hematology and Stem Cell Transplantation The Alfred Hospital Melbourne Victoria Australia

Department of Medical Oncology and Hematology HOCH Health Ostchweiz St Gallen Switzerland

Department of Oncology Hematology and BMT University Medical Center Hamburg Eppendorf Hamburg Germany

Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna Bologna Italy

Division of Genetics and Epidemiology The Institute of Cancer Research London UK

Faculty of Medicine University Hospital Ostrava Ostrava Czech Republic

Heidelberg Myeloma Center Department of Internal Medicine 5 Heidelberg University Hospital and Faculty Heidelberg Germany

Hematology Oncology Clinic Tartu University Tartu Estonia

INSERM UMR S1277 and CNRS UMR9020 Lille France

IRCCS Azienda Ospedaliero Universitaria di Bologna Istituto di Ematologia Seràgnoli Bologna Italy

Leeds Cancer Centre Leeds Teaching Hospitals NHS Trust Leeds UK

Leeds Institute of Clinical Trial Research University of Leeds Leeds UK

Oslo Myeloma Center Department of Hematology Oslo University Hospital Oslo Norway

Service d'Hématologie Clinique et de Thérapie Cellulaire Hôpital Saint Antoine AP HP Paris France

Université de Toulouse Centre Hospitalo Universitaire Institut Universitaire du Cancer Toulouse Oncopole Toulouse France

University Division of Hematology AOU Città della Salute e della Scienza di Torino Turin Italy

University Hospital of Salamanca IBSAL Cancer Research Center Salamanca Spain

Wilhelminen Cancer Research Institute 1st Department of Medicine Center for Oncology Hematology and Palliative Care Clinic Ottakring Vienna Austria

Zobrazit více v PubMed

Malard, F. et al. Multiple myeloma. Nat. Rev. Dis. Prim. 10, 45 (2024). PubMed DOI

Sun, et al. Global landscape and trends in lifetime risks of haematologic malignancies in 185 countries: population-based estimates from GLOBOCAN 2022. eClinicalMedicine 83, 103193 (2025). PubMed DOI PMC

Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 73, 17–48 (2023). PubMed DOI

Sonneveld, P. et al. Consolidation treatment with VRD followed by maintenance with lenalidomide in multiple myeloma improves overall survival: long-term follow-up of the EMN02/HOVON95 randomized phase 3 trial. Blood 144, 674–674 (2024). DOI

Surveillance, Epidemiology, and End Results Program. Cancer stat facts: myeloma. NIH https://seer.cancer.gov/statfacts/html/mulmy.html (2024).

Engelhardt, M., Kortum, K. M., Goldschmidt, H. & Merz, M. Functional cure and long-term survival in multiple myeloma: how to challenge the previously impossible. Haematologica 109, 2420–2435 (2024). PubMed PMC

Martinez-Lopez, J. et al. Real-world treatment patterns, healthcare resource use and disease burden in patients with multiple myeloma in Europe. Future Oncol. 19, 2103–2121 (2023). PubMed DOI

Rajkumar, S. V., Kumar, S., Lonial, S. & Mateos, M. V. Smoldering multiple myeloma current treatment algorithms. Blood Cancer J. 12, 129 (2022). PubMed DOI PMC

International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br. J. Haematol. 121, 749–757 (2003). DOI

Thorsteinsdóttir, S. et al. Prevalence of smoldering multiple myeloma based on nationwide screening. Nat. Med. 29, 467–472 (2023). PubMed DOI PMC

Dimopoulos, M. A. et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 32, 309–322 (2021). PubMed DOI

Dimopoulos, M. A. et al. Multiple myeloma: EHA-ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Hemasphere 5, e528 (2021). PubMed PMC

D’Agostino, M. et al. 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. J. Clin. Oncol. 40, 3406–3418 (2022). PubMed DOI

Palumbo, A. et al. Revised international staging system for multiple myeloma: a report from International Myeloma Working Group. J. Clin. Oncol. 33, 2863–2869 (2015). PubMed DOI PMC

Avet-Loiseau, H. et al. International Myeloma Society/International Myeloma Working Group consensus recommendations on the definition of high-risk multiple myeloma. J. Clin. Oncol., https://doi.org/10.1200/JCO-24-01893 (2025). PubMed DOI

Bertamini, L. et al. High levels of circulating tumor plasma cells as a key hallmark of aggressive disease in transplant-eligible patients with newly diagnosed multiple myeloma. J. Clin. Oncol. 40, 3120–3131 (2022). PubMed DOI

Garces, J. J. et al. Circulating tumor cells for the staging of patients with newly diagnosed transplant-eligible multiple myeloma. J. Clin. Oncol. 40, 3151–3161 (2022). PubMed DOI

Kostopoulos, I. V. et al. Circulating plasma cells in newly diagnosed multiple myeloma: prognostic and more. J. Clin. Oncol. 41, 708–710 (2023). PubMed DOI

Kostopoulos, I. V. et al. Low circulating tumor cell levels correlate with favorable outcomes and distinct biological features in multiple myeloma. Am. J. Hematol. 99, 1887–1896 (2024). PubMed DOI

Jelinek, T. et al. More than 2% of circulating tumor plasma cells defines plasma cell leukemia-like multiple myeloma. J. Clin. Oncol. 41, 1383–1392 (2023). PubMed DOI

Musto, P. et al. European Myeloma Network Group review and consensus statement on primary plasma cell leukemia. Ann. Oncol. 36, 361–374 (2025). PubMed DOI

Fernandez de Larrea, C. et al. Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage. Blood Cancer J. 11, 192 (2021). PubMed DOI PMC

Puig, N. et al. Mass spectrometry vs immunofixation for treatment monitoring in multiple myeloma. Blood Adv. 6, 3234–3239 (2022). PubMed DOI PMC

Giles, H. V. et al. Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry. Blood Cancer J. 14, 50 (2024). PubMed DOI PMC

Noori, S. et al. Dynamic monitoring of myeloma minimal residual disease with targeted mass spectrometry. Blood Cancer J. 13, 30 (2023). PubMed DOI PMC

Puig, N. et al. Measurable residual disease by mass spectrometry and next-generation flow to assess treatment response in myeloma. Blood 144, 2432–2438 (2024). PubMed DOI

Shah, V. et al. Predicting ultrahigh risk multiple myeloma by molecular profiling: an analysis of newly diagnosed transplant eligible myeloma XI trial patients. Leukemia 34, 3091–3096 (2020). PubMed DOI PMC

Skerget, S. et al. Comprehensive molecular profiling of multiple myeloma identifies refined copy number and expression subtypes. Nat. Genet. 56, 1878–1889 (2024). PubMed DOI PMC

Bhutani, M. et al. Investigation of a gene signature to predict response to immunomodulatory derivatives for patients with multiple myeloma: an exploratory, retrospective study using microarray datasets from prospective clinical trials. Lancet Haematol. 4, e443–e451 (2017). PubMed DOI

Kumar, S. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 17, e328–e346 (2016). PubMed DOI

Paiva, B. et al. Impact of treatment effect on MRD and PFS: an aggregate data analysis from randomized clinical trials in multiple myeloma. Blood Adv. 8, 219–223 (2024). PubMed DOI

Ntanasis-Stathopoulos, I. et al. Evaluating minimal residual disease negativity as a surrogate endpoint for treatment efficacy in multiple myeloma: a meta-analysis of randomized controlled trials. Am. J. Hematol. 100, 427–438 (2025). PubMed DOI PMC

Landgren, O. et al. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma. Blood 144, 359–367 (2024). PubMed DOI

Landgren, O. & Devlin, S. M. Minimal residual disease as an early endpoint for accelerated drug approval in myeloma: a roadmap. Blood Cancer Discov. 6, 13–22 (2025). PubMed DOI

Martinez-Lopez, J. et al. Measurable residual disease (MRD) dynamics in multiple myeloma and the influence of clonal diversity analyzed by artificial intelligence. Blood Cancer J. 14, 131 (2024). PubMed DOI PMC

Cavo, M. et al. Role of PubMed DOI

Rama, S. et al. Comparative performance of whole-body MRI and FDG PET/CT in evaluation of multiple myeloma treatment response: systematic review and meta-analysis. AJR Am. J. Roentgenol. 218, 602–613 (2022). PubMed DOI

Belotti, A. et al. Predictive role of sustained imaging MRD negativity assessed by diffusion-weighted whole-body MRI in multiple myeloma. Am. J. Hematol. 98, E230–E232 (2023). PubMed DOI

Ulaner, G. A., Lewis, J. & Landgren, O. CD38-targeted PubMed DOI

Pasquini, M. C. et al. Minimal residual disease status in multiple myeloma 1 year after autologous hematopoietic cell transplantation and lenalidomide maintenance are associated with long-term overall survival. J. Clin. Oncol. 42, 2757–2768 (2024). PubMed DOI

Derman, B. A. et al. Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP). Blood Cancer J. 14, 170 (2024). PubMed DOI PMC

Terpos, E. et al. Sustained MRD negativity for three years can guide discontinuation of lenalidomide maintenance after ASCT in multiple myeloma: results from a prospective cohort study. Blood https://doi.org/10.1182/blood-2024-209826 (2024). DOI

Radocha, J. et al. Urine immunofixation negativity is not necessary for complete response in intact immunoglobulin multiple myeloma: retrospective real-world confirmation. Int. J. Lab. Hematol. 43, e244–e247 (2021). PubMed DOI

Natsuhara, K. H. et al. Significance of the pee-value: relevance of 24-hour urine studies for patients with myeloma. Leuk. Lymphoma 64, 1186–1193 (2023). PubMed DOI

Mateos, M. V. et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 10, 102 (2020). PubMed DOI PMC

Schmidt, T. & Callander, N. Diagnosis and management of monoclonal gammopathy and smoldering multiple myeloma. J. Natl Compr. Canc Netw. 18, 1720–1729 (2020). PubMed DOI

Mateos, M. V. et al. Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: a randomized, open-label study. Eur. J. Cancer 174, 243–250 (2022). PubMed DOI

Lonial, S. et al. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J. Clin. Oncol. 38, 1126–1137 (2020). PubMed DOI

Landgren, C. O. et al. Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS). Leukemia 34, 1840–1852 (2020). PubMed DOI PMC

Landgren, O. et al. Efficacy and safety of daratumumab in intermediate/high-risk smoldering multiple myeloma: final analysis of CENTAURUS. Blood 145, 1658–1669 (2025). PubMed DOI

Dimopoulos, M. A. et al. Daratumumab or active monitoring for high-risk smoldering multiple myeloma. New Engl. J. Med. 392, 1777–1788 (2025). PubMed DOI

Mateos, M. V. et al. Curative strategy for high-risk smoldering myeloma: carfilzomib, lenalidomide, and dexamethasone (KRd) followed by transplant, KRd consolidation, and Rd maintenance. J. Clin. Oncol. 42, 3247–3256 (2024). PubMed DOI

Kazandjian, D. et al. Carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance for prevention of symptomatic multiple myeloma in patients with high-risk smoldering myeloma: a phase 2 nonrandomized controlled trial. JAMA Oncol. 7, 1678–1685 (2021). PubMed DOI

Kumar, S. K. et al. Fixed duration therapy with daratumumab, carfilzomib, lenalidomide and dexamethasone for high risk smoldering multiple myeloma – results of the ascent trial [abstract]. Blood 140, 1830–1832 (2022). DOI

Sonneveld, P. et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 390, 301–313 (2024). PubMed DOI

Badros, A. et al. Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study. Blood 145, 300–310 (2025). PubMed DOI

Mai, E. K. et al. Isatuximab, lenalidomide, bortezomib, and dexamethasone induction therapy for transplant-eligible newly diagnosed multiple myeloma: final part 1 analysis of the GMMG-HD7 trial. J. Clin. Oncol. 43, 1279–1288 (2025). PubMed DOI

Moreau, P. et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial. Lancet Oncol. 25, 1003–1014 (2024). PubMed DOI

Touzeau, C. et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma. Blood 143, 2029–2036 (2024). PubMed DOI

Costa, L. J. et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma. J. Clin. Oncol. 40, 2901–2912 (2022). PubMed DOI

Leypoldt, L. B. et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone for the treatment of high-risk newly diagnosed multiple myeloma. J. Clin. Oncol. 42, 26–37 (2024). PubMed DOI

Perrot, A. et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial. Blood https://doi.org/10.1182/blood.2024026230 (2025). PubMed DOI

Gay, F. et al. Results of the phase III randomized Iskia trial: isatuximab-carfilzomib-lenalidomide-dexamethasone vs carfilzomib-lenalidomide-dexamethasone as pre-transplant induction and post-transplant consolidation in newly diagnosed multiple myeloma patients [abstract]. Blood 142, 4 (2023). DOI

Kauer, J. et al. Stem cell collection after lenalidomide, bortezomib and dexamethasone plus elotuzumab or isatuximab in newly diagnosed multiple myeloma patients: a single centre experience from the GMMG-HD6 and -HD7 trials. BMC Cancer 23, 1132 (2023). PubMed DOI PMC

Mai, E. K. et al. Bortezomib before and after high-dose therapy in transplant-eligible patients with newly diagnosed multiple myeloma: long-term overall survival after more than 10 years of follow-up from the phase III HOVON-65/GMMG-HD4 trial. Hemasphere 8, e70052 (2024). PubMed DOI PMC

Cook, G. et al. Ixazomib as consolidation and maintenance versus observation in patients with relapsed multiple myeloma eligible for salvage autologous stem-cell transplantation (Myeloma XII [ACCoRD]): interim analysis of a multicentre, open-label, randomised, phase 3 trial. Lancet Haematol. 11, e816–e829 (2024). PubMed DOI

Dimopoulos, M. A. et al. Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial. Lancet 393, 253–264 (2019). PubMed DOI

Rosinol, L. et al. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood 142, 1518–1528 (2023). PubMed DOI

Krishnan, A. et al. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 12, 1195–1203 (2011). PubMed DOI PMC

Knop, S. et al. Allogeneic transplantation in multiple myeloma: long-term follow-up and cytogenetic subgroup analysis. Leukemia 33, 2710–2719 (2019). PubMed DOI

Kroger, N. et al. Autologous-allogeneic versus autologous tandem stem cell transplantation and maintenance therapy with thalidomide for multiple myeloma patients under 60 years of age: a prospective, phase II study. Haematologica 109, 1469–1479 (2024). PubMed

Facon et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N. Engl. J. Med. 380, 2104–2115 (2019). PubMed DOI PMC

Mateos, M. V. et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N. Engl. J. Med. 378, 518–528 (2018). PubMed DOI

Durie et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 389, 519–527 (2017). PubMed DOI

Facon, T. et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 391, 1597–1609 (2024). PubMed DOI

Leleu, X. et al. Isatuximab, lenalidomide, dexamethasone and bortezomib in transplant-ineligible multiple myeloma: the randomized phase 3 BENEFIT trial. Nat. Med. 30, 2235–2241 (2024). PubMed DOI PMC

Usmani, S. Z. et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS study. Nat. Med. 31, 1195–1202 (2025). PubMed DOI PMC

Mateos, M. V. et al. Bortezomib, melphalan, and prednisone with or without daratumumab in transplant-ineligible patients with newly diagnosed multiple myeloma (ALCYONE): final analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 26, 596–608 (2025). PubMed DOI

Fried, L. P. et al. From bedside to bench: research agenda for frailty. Sci. Aging Knowl. Env. 2005, pe24 (2005). DOI

Cook, G., Larocca, A., Facon, T., Zweegman, S. & Engelhardt, M. Defining the vulnerable patient with myeloma – a frailty position paper of the European Myeloma Network. Leukemia 34, 2285–2294 (2020). PubMed DOI PMC

Collard, R. M. et al. Prevalence of frailty in community-dwelling older persons: a systematic review. J. Am. Geriatr. Soc. 60, 1487–1492 (2012). PubMed DOI

Engelhardt, M. et al. A concise revised myeloma comorbidity index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients. Haematologica 102, 910–921 (2017). PubMed DOI PMC

Cook, G., Pawlyn, C., Cairns, D. A. & Jackson, G. H. Defining FiTNEss for treatment for multiple myeloma. Lancet Healthy Longev. 3, e729–e730 (2022). PubMed DOI

Palumbo, A. et al. Geriatric assessment predicts survival and toxicities in elderlymyeloma patients: an International Myeloma Working Group report. Blood 125, 2068–2074 (2015). PubMed DOI PMC

Haider, I. et al. Prevalence of geriatric impairments and frailty categorization among real-world patients with multiple myeloma: a prospective cohort study (MFRAIL). Leuk. Lymphoma 65, 1167–1174 (2024). PubMed DOI

Gahagan, A. et al. Evaluating concordance between International Myeloma Working Group (IMWG) frailty score and simplified frailty scale among older adults with multiple myeloma. J. Geriatr. Oncol. 15, 102051 (2024). PubMed DOI

Sim, S. et al. The importance of frailty assessment in multiple myeloma: a position statement from the Myeloma Scientific Advisory Group to Myeloma Australia. Intern. Med. J. 53, 819–824 (2023). PubMed DOI

Facon, T. et al. A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial. Leukemia 34, 224–233 (2020). PubMed DOI

Cook, G. et al. A clinical prediction model for outcome and therapy delivery in transplant-ineligible patients with myeloma (UK Myeloma Research Alliance risk profile): a development and validation study. Lancet Haematol. 6, e154–e166 (2019). PubMed DOI PMC

Cook, G. et al. IMWG frailty score-adjusted therapy delivery reduces the early mortality risk in newly diagnosed TNE multiple myeloma: results of the UK Myeloma ResearchAlliance (UK-MRA) myeloma XIV fitness trial [abstract]. Blood 144, 673 (2024). DOI

Facon, T. et al. Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA. Leukemia 36, 1066–1077 (2022). PubMed DOI PMC

Manier, S. et al. The IFM2017-03 phase 3 trial: a dexamethasone sparing-regimen with daratumumab and lenalidomide for frail patients with newly-diagnosed multiple myeloma [abstract]. Blood 144, 774–775 (2024). DOI

Askeland, F. B. et al. Isatuximab, bortezomib, lenalidomide, and limited dexamethasone in patients with transplant-ineligible multiple myeloma (REST): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 12, e120–e127 (2025). PubMed DOI

Hungria, V. et al. Belantamab mafodotin, bortezomib, and dexamethasone for multiple myeloma. N. Engl. J. Med. 391, 393–407 (2024). PubMed DOI

Hungria, V. et al. Belantamab mafodotin, bortezomib, and dexamethasone vs daratumumab, bortezomib, and dexamethasone in relapsed/refractory multiple myeloma: overall survival analysis and updated efficacy outcomes of the phase 3 dreamm-7 trial [abstract]. Blood 144, 772 (2024). DOI

San-Miguel, J. et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N. Engl. J. Med. 389, 335–347 (2023). PubMed DOI

Popat, R. et al. Ciltacabtagene autoleucel (Cilta-cel) vs standard of care (SoC) in patients with lenalidomide (Len)-refractory multiple myeloma (MM) after 1-3 lines of therapy: minimal residual disease (MRD) negativity in the phase 3 Cartitude-4 trial [abstract]. Blood 144, 1032 (2024). DOI

Dimopoulos, M. A. et al. Belantamab mafodotin, pomalidomide, and dexamethasone in multiple myeloma. N. Engl. J. Med. 391, 408–421 (2024). PubMed DOI

Trudel, S. et al. Results from the randomized phase 3 DREAMM-8 study of belantamab mafodotin plus pomalidomide and dexamethasone (BPd) vs pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM) [abstract]. J. Clin. Oncol. 42, LBA105 (2024). DOI

Grosicki, S. et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet 396, 1563–1573 (2020). PubMed DOI

Mateos, M. V. et al. Impact of prior treatment on selinexor, bortezomib, dexamethasone outcomes in patients with relapsed/refractory multiple myeloma: extended follow-up subgroup analysis of the BOSTON trial. Eur. J. Haematol. 113, 242–252 (2024). PubMed DOI

Gavriatopoulou, M. et al. Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials. Leukemia 34, 2430–2440 (2020). PubMed DOI PMC

Perrot, A. et al. An open-label phase 2 study treating patients with first or second relapse of multiple myeloma with carfilzomib, pomalidomide, and dexamethasone (KPd): SELECT study. Leuk. Lymphoma 65, 833–842 (2024). PubMed DOI

Sonneveld, P. et al. Carfilzomib, pomalidomide, and dexamethasone as second-line therapy for lenalidomide-refractory multiple myeloma. Hemasphere 6, e786 (2022). PubMed DOI PMC

Cavo, M. et al. Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Hematol. 7, e456–e468 (2020). DOI

Dimopoulos, M. A. et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 22, 801–812 (2021). PubMed DOI

Dimopoulos, M. A. et al. Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trial. Lancet Haematol. 10, e813–e824 (2023). PubMed DOI

Kastritis, E. et al. Management and outcomes of anti-CD38 refractory patients: the impact of retreatment and of subsequent therapies. Hemasphere 7, e975 (2023). PubMed DOI PMC

Perez de Acha, O. et al. CD38 antibody re-treatment in daratumumab-refractory multiple myeloma after time on other therapies. Blood Adv. 7, 6430–6440 (2023). PubMed DOI PMC

Usmani, S. Z. et al. Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study. Blood Adv. 7, 3739–3748 (2023). PubMed DOI PMC

Terpos, E. et al. Efficacy and safety of daratumumab with ixazomib and dexamethasone in lenalidomide-exposed patients after one prior line of therapy: final results of the phase 2 study DARIA. Am. J. Hematol. 99, 396–407 (2024). PubMed DOI

Martino, E. A. et al. Outcomes and prognostic indicators in daratumumab-refractory multiple myeloma: a multicenter real-world study of elotuzumab, pomalidomide, and dexamethasone in 247 patients. ESMO Open. 10, 104084 (2025). PubMed DOI PMC

Parrondo, R. D. et al. Phase II trial of elotuzumab with pomalidomide and dexamethasone for daratumumab-refractory multiple myeloma. Blood Cancer J. 14, 152 (2024). PubMed DOI PMC

Berdeja, J. G. et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 398, 314–324 (2021). PubMed DOI

Martin, T. et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J. Clin. Oncol. 41, 1265–1274 (2023). PubMed DOI

Munshi, N. C. et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 384, 705–716 (2021). PubMed DOI

Rodriguez-Otero, P. et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N. Engl. J. Med. 388, 1002–1014 (2023). PubMed DOI

Ailawadhi, S. et al. Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood 144, 2389–2401 (2024). PubMed DOI

Moreau, P. et al. Teclistamab in relapsed or refractory multiple myeloma. N. Engl. J. Med. 387, 495–505 (2022). PubMed DOI PMC

Garfall, A. L. et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma [abstract]. J. Clin. Oncol. 42, 7540 (2024). DOI

Lesokhin, A. M. et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat. Med. 29, 2259–2267 (2023). PubMed DOI PMC

Prince, H. M. et al. MagnetisMM-3: long-term update and efficacy and safety of less frequent dosing of elranatamab in patients with relapsed or refractory multiple myeloma [abstract]. Blood 144, 4738 (2024). DOI

Bumma, N. et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J. Clin. Oncol. 42, 2702–2712 (2024). PubMed DOI

Chari, A. et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N. Engl. J. Med. 387, 2232–2244 (2022). PubMed DOI

Chari, A. et al. Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1–2 study. Lancet Hematol. 12, e269–e281 (2025). DOI

Richardson, P. G. et al. Melflufen and dexamethasone in heavily pretreated relapsed and refractory multiple myeloma. J. Clin. Oncol. 39, 757–767 (2021). PubMed DOI

Schjesvold, F. H. et al. Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Lancet Haematol. 9, e98–e110 (2022). PubMed DOI

Costa, L. J. et al. International Myeloma Working Group Immunotherapy Committee recommendation on sequencing immunotherapy for treatment of multiple myeloma. Leukemia 39, 543–554 (2025). PubMed DOI PMC

Ferreri, C. J. et al. Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. Blood Cancer J. 13, 117 (2023). PubMed DOI PMC

Cohen, A. D. et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood 141, 219–230 (2023). PubMed DOI

Merz, M. et al. Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy. Blood Cancer J. 14, 214 (2024). PubMed DOI PMC

Nooka, A. K. et al. Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) and prior B-cell maturation antigen (BCMA)-directed therapies: a pooled analysis from MagnetisMM studies [abstract]. J. Clin. Oncol. 41, 8008 (2023). DOI

Touzeau, C. et al. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies. Blood 144, 2375–2388 (2024). PubMed DOI

Terpos, E., Ntanasis-Stathopoulos, I. & Dimopoulos, M. A. Myeloma bone disease: from biology findings to treatment approaches. Blood 133, 1534–1539 (2019). PubMed DOI

Terpos, E. et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 22, e119–e130 (2021). PubMed DOI

Terpos, E. et al. European Myeloma Network guidelines for the management of multiple myeloma-related complications. Haematologica 100, 1254–1266 (2015). PubMed DOI PMC

Anderson, K. et al. Role of bone-modifying agents in multiple myeloma: American Society of Clinical Oncology clinical practice guideline update. J. Clin. Oncol. 36, 812–818 (2018). PubMed DOI

Raje, N. et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 19, 370–381 (2018). PubMed DOI

Terpos, E. et al. Denosumab compared with zoledronic acid on PFS in multiple myeloma: exploratory results of an international phase 3 study. Blood Adv. 5, 725–736 (2021). PubMed DOI PMC

Terpos, E. et al. Evaluation of the safety and efficacy of denosumab in patients with multiple myeloma and severe renal impairment; results from an IMWG Bone Subcommittee study [abstract]. Blood 144, 3343–3344 (2024). DOI

Larocca, A. et al. The impact of response on bone-directed therapy in patients with multiple myeloma. Blood 122, 2974–2977 (2013). PubMed DOI

Lund, T. et al. In multiple myeloma, monthly treatment with zoledronic acid beyond two years offers sustained protection against progressive bone disease. Blood Cancer J. 14, 65 (2024). PubMed DOI PMC

Katodritou, E. et al. Update on the use of erythropoiesis-stimulating agents (ESAs) for the management of anemia of multiple myeloma and lymphoma. Cancer Treat. Rev. 35, 738–743 (2009). PubMed DOI

Terpos, E. et al. Management of complications in multiple myeloma. Semin. Hematol. 46, 176–189 (2009). PubMed DOI

Blimark, C. et al. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients. Haematologica 100, 107–113 (2015). PubMed DOI PMC

Raje, N. S. et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 9, e143–e161 (2022). PubMed DOI

Ludwig, H. et al. Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network. Leukemia 35, 31–44 (2021). PubMed DOI

Raje, N. et al. Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel. Blood Cancer J. 13, 116 (2023). PubMed DOI PMC

Drayson, M. T. et al. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol. 20, 1760–1772 (2019). PubMed DOI PMC

Dimopoulos, M. A. et al. Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group. Lancet Oncol. 24, e293–e311 (2023). PubMed DOI

Mikhael, J. et al. Lenalidomide and dexamethasone in patients with relapsed multiple myeloma and impaired renal function: PrE1003, a PrECOG study. Blood Cancer J. 8, 86 (2018). PubMed DOI PMC

Dimopoulos, M. A. et al. Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents. Ann. Oncol. 25, 195–200 (2014). PubMed DOI

Cejalvo, M. J. et al. Single-agent daratumumab in patients with relapsed and refractory multiple myeloma requiring dialysis: results of a Spanish retrospective, multicentre study. Br. J. Haematol. 190, e289–e292 (2020). PubMed DOI

Kastritis, E. et al. Prospective phase 2 trial of daratumumab with dexamethasone in patients with relapsed/refractory multiple myeloma and severe renal impairment or on dialysis: the DARE study. Am. J. Hematol. 98, E226–E229 (2023). PubMed DOI

Wasch, R. et al. Safe and successful CAR T-cell therapy targeting BCMA in a multiple myeloma patient requiring hemodialysis. Ann. Hematol. 102, 1269–1270 (2023). PubMed DOI PMC

Joiner, L., Bal, S., Godby, K. N. & Costa, L. J. Teclistamab in patients with multiple myeloma and impaired renal function. Am. J. Hematol. 98, E322–E324 (2023). PubMed DOI

Lebreton, P. et al. Teclistamab for relapsed refractory multiple myeloma patients on dialysis. Br. J. Haematol. 205, 2077–2079 (2024). PubMed DOI

Lonial, S. et al. Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM). Blood Cancer J. 11, 103 (2021). PubMed DOI PMC

Terpos, E. et al. Belantamab mafodotin plus lenalidomide/dexamethasone in newly diagnosed intermediate-fit and frail multiple myeloma patients: long-term efficacy and safety from the phase 1/2 BELARD clinical trial [abstract]. J. Clin. Oncol. https://doi.org/10.1200/JCO.2025.43.16_suppl.7512 (2025). DOI

Li, J. et al. CD3 bispecific antibody-induced cytokine release is dispensable for cytotoxic T cell activity. Sci. Transl. Med. 11, eaax8861 (2019). PubMed DOI

Ludwig, H. et al. Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Lancet Oncol. 24, e255–e269 (2023). PubMed DOI

Han, M. W. et al. Incidence of immune effector cell-associated neurotoxicity among patients treated with CAR T-cell therapy for hematologic malignancies: systematic review and meta-analysis. Front. Neurol. 15, 1392831 (2024). PubMed DOI PMC

Brudno, J. N. & Kochenderfer, J. N. Recent advances in CAR T-cell toxicity: mechanisms, manifestations and management. Blood Rev. 34, 45–55 (2019). PubMed DOI

Santomasso, B. D. et al. Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov. 8, 958–971 (2018). PubMed DOI PMC

Van Oekelen, O. et al. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nat. Med. 27, 2099–2103 (2021). PubMed DOI PMC

Morris, E. C., Neelapu, S. S., Giavridis, T. & Sadelain, M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat. Rev. Immunol. 22, 85–96 (2022). PubMed DOI

Costa, B. A. et al. Prognostic impact of corticosteroid and tocilizumab use following chimeric antigen receptor T-cell therapy for multiple myeloma. Blood Cancer J. 14, 84 (2024). PubMed DOI PMC

Jatiani, S. S. et al. Myeloma CAR-T CRS management with IL-1R antagonist anakinra. Clin. Lymphoma Myeloma Leuk. 20, 632–636.e1 (2020). PubMed DOI PMC

Kumar, S. K. et al. NCCN guidelines insights: multiple myeloma, version 1.2025. J. Natl Compr. Canc Netw. 23, 132–140 (2025). PubMed DOI

Gross, P. A. et al. Purpose of quality standards for infectious diseases. Clin. Infect. Dis. 18, 421 (1994). PubMed DOI

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