多发性骨髓瘤识别与治疗：从骨痛贫血到复发难治新药

先看懂四件事：怎么识别、怎么确诊、怎么治疗、怎么长期管理Multiple Myeloma

多发性骨髓瘤是浆细胞恶性克隆性疾病，起病隐匿，常以骨痛、贫血、肾功能异常或反复感染就诊。诊断依据 IMWG 标准，既包括高钙、肾功能损害、贫血与骨病（CRAB），也包括骨髓浆细胞比例、血清游离轻链比值与影像学发现的特定生物标志物。治疗已从单一方案走向「诱导治疗、自体移植、维持治疗、复发后换方案」的长期管理。

发病机理：浆细胞异常增殖与器官损害的连锁反应Pathogenesis

骨髓瘤的危害不只来自肿瘤本身：异常浆细胞抑制正常造血、分泌单克隆免疫球蛋白与轻链损伤肾脏、激活破骨细胞造成溶骨性病变，这三条路径共同决定了贫血、肾损害、骨痛与反复感染的临床表现。

哪些情况提示需要检查骨髓瘤

两个容易被忽略的问题

怎么检查：血液、尿液、骨髓与影像Assessment

怎么治疗：初始、移植、骨病与复发难治Treatment

治疗与支持管理一览

日常管理：感染、肾脏与疼痛Daily Management

十个常见误区Ten Common Misconceptions

参考文献与证据来源References & Evidence

本页共 24 条文献，来自国际共识与指南、随机对照试验、荟萃分析与机制研究，链接指向 PubMed。每条结论后的编号对应下方文献；证据不足或结论不一致之处已在正文标注。

1. IMWG 共识（多发性骨髓瘤诊断标准的更新）Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosinol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksac M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. The Lancet. Oncology. 2014;15(12):e538-48. pubmed.ncbi.nlm.nih.gov/25439696
2. IMWG 共识建议（多发性骨髓瘤的感染预防）Raje NS, Anaissie E, Kumar SK, Lonial S, Martin T, Gertz MA, Krishnan A, Hari P, Ludwig H, O'Donnell E, Yee A, Kaufman JL, Cohen AD, Garderet L, Wechalekar AF, Terpos E, Khatry N, Niesvizky R, Yi Q, Joshua DE, Saikia T, Leung N, Engelhardt M, Mothy M, Branagan A, Chari A, Reiman AJ, Lipe B, Richter J, Rajkumar SV, Miguel JS, Anderson KC, Stadtmauer EA, Prabhala RH, McCarthy PL, Munshi NC. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. The Lancet. Haematology. 2022;9(2):e143-e161. pubmed.ncbi.nlm.nih.gov/35114152
3. IMWG 建议（多发性骨髓瘤相关肾损害的管理）Dimopoulos MA, Merlini G, Bridoux F, Leung N, Mikhael J, Harrison SJ, Kastritis E, Garderet L, Gozzetti A, van de Donk NWCJ, Weisel KC, Badros AZ, Beksac M, Hillengass J, Mohty M, Ho PJ, Ntanasis-Stathopoulos I, Mateos MV, Richardson P, Blade J, Moreau P, San-Miguel J, Munshi N, Rajkumar SV, Durie BGM, Ludwig H, Terpos E, International Myeloma Working Group. Management of multiple myeloma-related renal impairment: recommendations from the International Myeloma Working Group. The Lancet. Oncology. 2023;24(7):e293-e311. pubmed.ncbi.nlm.nih.gov/37414019
4. IMWG 骨工作组建议（多发性骨髓瘤相关骨病的治疗）Terpos E, Zamagni E, Lentzsch S, Drake MT, García-Sanz R, Abildgaard N, Ntanasis-Stathopoulos I, Schjesvold F, de la Rubia J, Kyriakou C, Hillengass J, Zweegman S, Cavo M, Moreau P, San-Miguel J, Dimopoulos MA, Munshi N, Durie BGM, Raje N, Bone Working Group of the International Myeloma Working Group. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. The Lancet. Oncology. 2021;22(3):e119-e130. pubmed.ncbi.nlm.nih.gov/33545067
5. IMWG 共识标准（多发性骨髓瘤的疗效与微小残留病灶评估）Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. The Lancet. Oncology. 2016;17(8):e328-e346. pubmed.ncbi.nlm.nih.gov/27511158
6. ASCO 指南（成人癌症患者的疫苗接种）Kamboj M, Bohlke K, Baptiste DM, Dunleavy K, Fueger A, Jones L, Kelkar AH, Law LY, LeFebvre KB, Ljungman P, Miller ED, Meyer LA, Moore HN, Soares HP, Taplitz RA, Woldetsadik ES, Kohn EC. Vaccination of Adults With Cancer: ASCO Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024;42(14):1699-1721. pubmed.ncbi.nlm.nih.gov/38498792
7. 随机Ⅲ期试验（硼替佐米联合来那度胺与地塞米松治疗新诊断骨髓瘤：SWOG S0777）Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. 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 (London, England). 2017;389(10068):519-527. pubmed.ncbi.nlm.nih.gov/28017406
8. 随机Ⅲ期试验（达雷妥尤单抗联合方案治疗新诊断骨髓瘤的总生存：ALCYONE）Mateos MV, Cavo M, Blade J, Dimopoulos MA, Suzuki K, Jakubowiak A, Knop S, Doyen C, Lucio P, Nagy Z, Pour L, Cook M, Grosicki S, Crepaldi A, Liberati AM, Campbell P, Shelekhova T, Yoon SS, Iosava G, Fujisaki T, Garg M, Krevvata M, Chen Y, Wang J, Kudva A, Ukropec J, Wroblewski S, Qi M, Kobos R, San-Miguel J. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. Lancet (London, England). 2020;395(10218):132-141. pubmed.ncbi.nlm.nih.gov/31836199
9. 随机Ⅲ期试验长期结局（达雷妥尤单抗联合来那度胺与地塞米松治疗不适合移植的新诊断骨髓瘤：MAIA）Facon T, Moreau P, Weisel K, Goldschmidt H, Usmani SZ, Chari A, Plesner T, Orlowski RZ, Bahlis N, Basu S, Hulin C, Quach H, O'Dwyer M, Perrot A, Jacquet C, Venner CP, Raje N, Tiab M, Macro M, Frenzel L, Leleu X, Cook G, Wang G, Pei H, Krevvata M, Carson R, Borgsten F, Kumar SK. Daratumumab/lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma: MAIA long-term outcomes. Leukemia. 2025;39(4):942-950. pubmed.ncbi.nlm.nih.gov/40016302
10. 随机Ⅲ期试验（三联治疗、移植与维持治疗至进展：DETERMINATION）Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC, DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. The New England journal of medicine. 2022;387(2):132-147. pubmed.ncbi.nlm.nih.gov/35660812
11. 随机开放标签Ⅱ期试验（卡非佐米为基础的方案与自体移植策略：FORTE）Gay F, Musto P, Rota-Scalabrini D, Bertamini L, Belotti A, Galli M, Offidani M, Zamagni E, Ledda A, Grasso M, Ballanti S, Spadano A, Cea M, Patriarca F, D'Agostino M, Capra A, Giuliani N, de Fabritiis P, Aquino S, Palmas A, Gamberi B, Zambello R, Petrucci MT, Corradini P, Cavo M, Boccadoro M. Carfilzomib with cyclophosphamide and dexamethasone or lenalidomide and dexamethasone plus autologous transplantation or carfilzomib plus lenalidomide and dexamethasone, followed by maintenance with carfilzomib plus lenalidomide or lenalidomide alone for patients with newly diagnosed multiple myeloma (FORTE): a randomised, open-label, phase 2 trial. The Lancet. Oncology. 2021;22(12):1705-1720. pubmed.ncbi.nlm.nih.gov/34774221
12. 随机双盲双模拟Ⅲ期试验（地舒单抗与唑来膦酸治疗新诊断骨髓瘤骨病）Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, Legieć W, Krejčí M, Laribi K, Zhu L, Cheng P, Warner D, Roodman GD. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. The Lancet. Oncology. 2018;19(3):370-381. pubmed.ncbi.nlm.nih.gov/29429912
13. 随机对照试验（唑来膦酸与氯膦酸一线治疗骨髓瘤：MRC Myeloma IX）Morgan GJ, Davies FE, Gregory WM, Cocks K, Bell SE, Szubert AJ, Navarro-Coy N, Drayson MT, Owen RG, Feyler S, Ashcroft AJ, Ross F, Byrne J, Roddie H, Rudin C, Cook G, Jackson GH, Child JA, National Cancer Research Institute Haematological Oncology Clinical Study Group. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet (London, England). 2010;376(9757):1989-1999. pubmed.ncbi.nlm.nih.gov/21131037
14. 随机Ⅲ期试验（ide-cel 与标准方案治疗复发难治骨髓瘤：KarMMa-3）Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, Manier S, Callander N, Costa LJ, Vij R, Bahlis NJ, Moreau P, Solomon SR, Delforge M, Berdeja J, Truppel-Hartmann A, Yang Z, Favre-Kontula L, Wu F, Piasecki J, Cook M, Giralt S. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. The New England journal of medicine. 2023;388(11):1002-1014. pubmed.ncbi.nlm.nih.gov/36762851
15. 随机Ⅲ期试验（西达基奥仑赛与标准治疗用于来那度胺难治骨髓瘤：CARTITUDE-4）San-Miguel J, Dhakal B, Yong K, Spencer A, Anguille S, Mateos MV, Fernández de Larrea C, Martínez-López J, Martínez-López J, Moreau P, Touzeau C, Leleu X, Avivi I, Cavo M, Ishida T, Kim SJ, Roeloffzen W, van de Donk NWCJ, Dytfeld D, Sidana S, Costa LJ, Oriol A, Popat R, Khan AM, Cohen YC, Ho PJ, Griffin J, Lendvai N, Lonardi C, Slaughter A, Schecter JM, Jackson CC, Connors K, Li K, Zudaire E, Chen D, Gilbert J, Yeh TM, Nagle S, Florendo E, Pacaud L, Patel N, Harrison SJ, Einsele H. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. The New England journal of medicine. 2023;389(4):335-347. pubmed.ncbi.nlm.nih.gov/37272512
16. 随机Ⅲ期试验（特立妥单抗联合达雷妥尤单抗治疗复发难治骨髓瘤：MajesTEC-3）Costa LJ, Bahlis NJ, Perrot A, Nooka AK, Lu J, Pawlyn C, Mina R, Caeiro G, Kentos A, Hungria V, Reece D, Niu T, Mylin AK, Hansen CT, Teipel R, Besemer B, Dimopoulos MA, Zamagni E, Yoshihara S, Kim K, Min CK, Geerts P, Van Leeuwen-Segarceanu E, Tyczynska A, Reguera JL, Johansson M, Hansson M, Turgut M, Grey M, Sidana S, Rodriguez-Otero P, Martinez-Lopez J, Hashmi H, Carson R, Kobos R, Sun W, Lantz K, Seifert A, Briseno-Toomey D, O'Rourke L, Rubin M, Vieyra D, Kang L, Mateos MV, MajesTEC-3 Trial Investigators. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. The New England journal of medicine. 2026;394(8):739-752. pubmed.ncbi.nlm.nih.gov/41363801
17. 随机Ⅲ期试验（达雷妥尤单抗与积极监测用于高危冒烟型骨髓瘤）Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, Lindsay J, Baker RI, Suzuki K, Kosugi H, Levin MD, Beksac M, Stockerl-Goldstein K, Oriol A, Mikala G, Garate G, Theunissen K, Spicka I, Mylin AK, Bringhen S, Uttervall K, Pula B, Medvedova E, Cowan AJ, Moreau P, Mateos MV, Goldschmidt H, Ahmadi T, Sha L, Cortoos A, Katz EG, Rousseau E, Li L, Dennis RM, Carson R, Rajkumar SV, AQUILA Investigators. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. The New England journal of medicine. 2025;392(18):1777-1788. pubmed.ncbi.nlm.nih.gov/39652675
18. 荟萃分析（微小残留病灶作为骨髓瘤中间临床终点的评价：EVIDENCE）Landgren O, Prior TJ, Masterson T, Heuck C, Bueno OF, Dash AB, Einsele H, Goldschmidt H, Knop S, Li C, Mellqvist UH, McFadden I, Oprea C, Ross JA, Talpes M, Hydren JR, Ahlstrom JM, Kazandjian D, Weinhold N, Zhang R, Stetler-Stevenson M, Marti G, Devlin SM. EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma. Blood. 2024;144(4):359-367. pubmed.ncbi.nlm.nih.gov/38768337
19. 系统评价与荟萃分析（地舒单抗与唑来膦酸治疗转移性骨病）Wajda BG, Ferrie LE, Abbott AG, Elmi Assadzadeh G, Monument MJ, Kendal JK. Denosumab vs. Zoledronic Acid for Metastatic Bone Disease: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials. Cancers. 2025;17(3):388. pubmed.ncbi.nlm.nih.gov/39941757
20. 长期随访队列研究（意义未明的单克隆丙种球蛋白病）Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, Rajkumar SV. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. The New England journal of medicine. 2018;378(3):241-249. pubmed.ncbi.nlm.nih.gov/29342381
21. IMWG 风险分层模型（冒烟型多发性骨髓瘤）Mateos MV, Kumar S, Dimopoulos MA, González-Calle V, Kastritis E, Hajek R, De Larrea CF, Morgan GJ, Merlini G, Goldschmidt H, Geraldes C, Gozzetti A, Kyriakou C, Garderet L, Hansson M, Zamagni E, Fantl D, Leleu X, Kim BS, Esteves G, Ludwig H, Usmani S, Min CK, Qi M, Ukropec J, Weiss BM, Rajkumar SV, Durie BGM, San-Miguel J. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood cancer journal. 2020;10(10):102. pubmed.ncbi.nlm.nih.gov/33067414
22. 疾病负担分析（2006–2016 年中国多发性骨髓瘤的发病与死亡）Liu J, Liu W, Mi L, Zeng X, Cai C, Ma J, Wang L, Union for China Lymphoma Investigators of the Chinese Society of Clinical Oncology, Union for China Leukemia Investigators of the Chinese Society of Clinical Oncology. Incidence and mortality of multiple myeloma in China, 2006-2016: an analysis of the Global Burden of Disease Study 2016. Journal of hematology & oncology. 2019;12(1):136. pubmed.ncbi.nlm.nih.gov/31823802
23. 疾病负担研究（1990–2019 年全球、区域与国家多发性骨髓瘤负担）Zhou L, Yu Q, Wei G, Wang L, Huang Y, Hu K, Hu Y, Huang H. Measuring the global, regional, and national burden of multiple myeloma from 1990 to 2019. BMC cancer. 2021;21(1):606. pubmed.ncbi.nlm.nih.gov/34034700
24. 人群调查研究（中国深圳人群意义未明的单克隆丙种球蛋白病患病率）Xu A, Guo T, Zhang S, Luo H, Shen M, Ye Y, Ji L. Prevalence of monoclonal gammopathy of undetermined significance in Shenzhen, China. Hematology (Amsterdam, Netherlands). 2024;29(1):2352686. pubmed.ncbi.nlm.nih.gov/38819332