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ISS Stage III Multiple Myeloma

MedGen UID:
384538
•Concept ID:
C2346456
•
Neoplastic Process
Synonyms: International Staging System Stage III Multiple Myeloma; International Staging System Stage III Plasma Cell Myeloma; ISS Stage III Plasma Cell Myeloma; Multiple Myeloma Stage III; Stage III Multiple Myeloma; Stage III Plasma Cell Myeloma

Definition

Multiple myeloma with beta-2-microglobulin greater than or equal to 5.5 (median survival of 29 months). Note that the older Durie/Salmon staging system defines stage III quite differently. (PDQ) [from NCI]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVISS Stage III Multiple Myeloma

Professional guidelines

PubMed

Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis.
Lin CM, Chang LC, Shau WY, Chen CL, Yao CY, Tien FM
BMC Cancer 2023 May 16;23(1):446. doi: 10.1186/s12885-023-10907-1. PMID: 37193978Free PMC Article
The evolving diagnosis and treatment paradigms of multiple myeloma in China: 15 years' experience of 1256 patients in a national medical center.
Yang Y, Li J, Wang W, Wang Y, Maihemaiti A, Ren L, Lan T, Zhou C, Li P, Wang P, Aihemaiti X, Chen F, Xu T, Xu J, Liu P
Cancer Med 2023 Apr;12(8):9604-9614. Epub 2023 Feb 21 doi: 10.1002/cam4.5737. PMID: 36807775Free PMC Article
Diagnosis and treatment of multiple myeloma in Hunan Province.
Liu F, Cheng Q, Song K, Yu H, Li J, Zhang H, Hu G, Zhou M, Wang J, Ding Z, Luo Z, Peng T, Ding L, Zhao L, Liu J, He Y, Peng H
Zhong Nan Da Xue Xue Bao Yi Xue Ban 2022 Apr 28;47(4):497-504. doi: 10.11817/j.issn.1672-7347.2022.210555. PMID: 35545345Free PMC Article

Recent clinical studies

Etiology

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.
D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall'Olio D, van de Donk NWCJ, Jackson G, Rocchi S, Salwender H, Bladé Creixenti J, van der Holt B, Castellani G, Bonello F, Capra A, Mai EK, Dürig J, Gay F, Zweegman S, Cavo M, Kaiser MF, Goldschmidt H, Hernández Rivas JM, Larocca A, Cook G, San-Miguel JF, Boccadoro M, Sonneveld P
J Clin Oncol 2022 Oct 10;40(29):3406-3418. Epub 2022 May 23 doi: 10.1200/JCO.21.02614. PMID: 35605179
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.
Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P
Lancet Haematol 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30 doi: 10.1016/S2352-3026(20)30099-5. PMID: 32359506
CD27 antigen negative expression indicates poor prognosis in newly diagnosed multiple myeloma.
Chu B, Bao L, Wang Y, Lu M, Shi L, Gao S, Fang L, Xiang Q, Liu X
Clin Immunol 2020 Apr;213:108363. Epub 2020 Feb 29 doi: 10.1016/j.clim.2020.108363. PMID: 32120013
Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group.
Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P
J Clin Oncol 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3 doi: 10.1200/JCO.2015.61.2267. PMID: 26240224Free PMC Article
International staging system for multiple myeloma.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J
J Clin Oncol 2005 May 20;23(15):3412-20. Epub 2005 Apr 4 doi: 10.1200/JCO.2005.04.242. PMID: 15809451

Diagnosis

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.
D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall'Olio D, van de Donk NWCJ, Jackson G, Rocchi S, Salwender H, Bladé Creixenti J, van der Holt B, Castellani G, Bonello F, Capra A, Mai EK, Dürig J, Gay F, Zweegman S, Cavo M, Kaiser MF, Goldschmidt H, Hernández Rivas JM, Larocca A, Cook G, San-Miguel JF, Boccadoro M, Sonneveld P
J Clin Oncol 2022 Oct 10;40(29):3406-3418. Epub 2022 May 23 doi: 10.1200/JCO.21.02614. PMID: 35605179
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.
Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P
Lancet Haematol 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30 doi: 10.1016/S2352-3026(20)30099-5. PMID: 32359506
CD27 antigen negative expression indicates poor prognosis in newly diagnosed multiple myeloma.
Chu B, Bao L, Wang Y, Lu M, Shi L, Gao S, Fang L, Xiang Q, Liu X
Clin Immunol 2020 Apr;213:108363. Epub 2020 Feb 29 doi: 10.1016/j.clim.2020.108363. PMID: 32120013
Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group.
Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P
J Clin Oncol 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3 doi: 10.1200/JCO.2015.61.2267. PMID: 26240224Free PMC Article
International staging system for multiple myeloma.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J
J Clin Oncol 2005 May 20;23(15):3412-20. Epub 2005 Apr 4 doi: 10.1200/JCO.2005.04.242. PMID: 15809451

Therapy

Population Pharmacokinetics and Exposure-Response with Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma: Results From MajesTEC-1.
Miao X, Wu LS, Lin SXW, Xu Y, Chen Y, Iwaki Y, Kobos R, Stephenson T, Kemmerer K, Uhlar CM, Banerjee A, Goldberg JD, Trancucci D, Apte A, Verona R, Pei L, Desai R, Hickey K, Su Y, Ouellet D, Samtani MN, Guo Y, Garfall AL, Krishnan A, Usmani SZ, Zhou H, Girgis S
Target Oncol 2023 Sep;18(5):667-684. Epub 2023 Sep 15 doi: 10.1007/s11523-023-00989-z. PMID: 37713090Free PMC Article
Consolidation and Maintenance in Newly Diagnosed Multiple Myeloma.
Sonneveld P, Dimopoulos MA, Beksac M, van der Holt B, Aquino S, Ludwig H, Zweegman S, Zander T, Zamagni E, Wester R, Hajek R, Pantani L, Dozza L, Gay F, Cafro A, De Rosa L, Morelli A, Gregersen H, Gulbrandsen N, Cornelisse P, Troia R, Oliva S, van de Velden V, Wu K, Ypma PF, Bos G, Levin MD, Pour L, Driessen C, Broijl A, Croockewit A, Minnema MC, Waage A, Hveding C, van de Donk NWCJ, Offidani M, Palumbo GA, Spencer A, Boccadoro M, Cavo M
J Clin Oncol 2021 Nov 10;39(32):3613-3622. Epub 2021 Sep 14 doi: 10.1200/JCO.21.01045. PMID: 34520219
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.
Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P
Lancet Haematol 2020 Jun;7(6):e456-e468. Epub 2020 Apr 30 doi: 10.1016/S2352-3026(20)30099-5. PMID: 32359506
A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial.
Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J
Leukemia 2020 Jan;34(1):224-233. Epub 2019 Aug 19 doi: 10.1038/s41375-019-0539-0. PMID: 31427722Free PMC Article
Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial.
Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM
J Clin Oncol 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16 doi: 10.1200/JCO.2011.39.6820. PMID: 22802322

Prognosis

Population Pharmacokinetics and Exposure-Response with Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma: Results From MajesTEC-1.
Miao X, Wu LS, Lin SXW, Xu Y, Chen Y, Iwaki Y, Kobos R, Stephenson T, Kemmerer K, Uhlar CM, Banerjee A, Goldberg JD, Trancucci D, Apte A, Verona R, Pei L, Desai R, Hickey K, Su Y, Ouellet D, Samtani MN, Guo Y, Garfall AL, Krishnan A, Usmani SZ, Zhou H, Girgis S
Target Oncol 2023 Sep;18(5):667-684. Epub 2023 Sep 15 doi: 10.1007/s11523-023-00989-z. PMID: 37713090Free PMC Article
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.
D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall'Olio D, van de Donk NWCJ, Jackson G, Rocchi S, Salwender H, Bladé Creixenti J, van der Holt B, Castellani G, Bonello F, Capra A, Mai EK, Dürig J, Gay F, Zweegman S, Cavo M, Kaiser MF, Goldschmidt H, Hernández Rivas JM, Larocca A, Cook G, San-Miguel JF, Boccadoro M, Sonneveld P
J Clin Oncol 2022 Oct 10;40(29):3406-3418. Epub 2022 May 23 doi: 10.1200/JCO.21.02614. PMID: 35605179
A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial.
Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J
Leukemia 2020 Jan;34(1):224-233. Epub 2019 Aug 19 doi: 10.1038/s41375-019-0539-0. PMID: 31427722Free PMC Article
Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group.
Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P
J Clin Oncol 2015 Sep 10;33(26):2863-9. Epub 2015 Aug 3 doi: 10.1200/JCO.2015.61.2267. PMID: 26240224Free PMC Article
International staging system for multiple myeloma.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J
J Clin Oncol 2005 May 20;23(15):3412-20. Epub 2005 Apr 4 doi: 10.1200/JCO.2005.04.242. PMID: 15809451

Clinical prediction guides

Population Pharmacokinetics and Exposure-Response with Teclistamab in Patients With Relapsed/Refractory Multiple Myeloma: Results From MajesTEC-1.
Miao X, Wu LS, Lin SXW, Xu Y, Chen Y, Iwaki Y, Kobos R, Stephenson T, Kemmerer K, Uhlar CM, Banerjee A, Goldberg JD, Trancucci D, Apte A, Verona R, Pei L, Desai R, Hickey K, Su Y, Ouellet D, Samtani MN, Guo Y, Garfall AL, Krishnan A, Usmani SZ, Zhou H, Girgis S
Target Oncol 2023 Sep;18(5):667-684. Epub 2023 Sep 15 doi: 10.1007/s11523-023-00989-z. PMID: 37713090Free PMC Article
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.
D'Agostino M, Cairns DA, Lahuerta JJ, Wester R, Bertsch U, Waage A, Zamagni E, Mateos MV, Dall'Olio D, van de Donk NWCJ, Jackson G, Rocchi S, Salwender H, Bladé Creixenti J, van der Holt B, Castellani G, Bonello F, Capra A, Mai EK, Dürig J, Gay F, Zweegman S, Cavo M, Kaiser MF, Goldschmidt H, Hernández Rivas JM, Larocca A, Cook G, San-Miguel JF, Boccadoro M, Sonneveld P
J Clin Oncol 2022 Oct 10;40(29):3406-3418. Epub 2022 May 23 doi: 10.1200/JCO.21.02614. PMID: 35605179
A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial.
Facon T, Dimopoulos MA, Meuleman N, Belch A, Mohty M, Chen WM, Kim K, Zamagni E, Rodriguez-Otero P, Renwick W, Rose C, Tempescul A, Boyle E, Manier S, Attal M, Moreau P, Macro M, Leleu X, Lorraine Chretien M, Ludwig H, Guo S, Sturniolo M, Tinel A, Silvia Monzini M, Costa B, Houck V, Hulin C, Yves Mary J
Leukemia 2020 Jan;34(1):224-233. Epub 2019 Aug 19 doi: 10.1038/s41375-019-0539-0. PMID: 31427722Free PMC Article
Bortezomib induction and maintenance treatment in patients with newly diagnosed multiple myeloma: results of the randomized phase III HOVON-65/ GMMG-HD4 trial.
Sonneveld P, Schmidt-Wolf IG, van der Holt B, El Jarari L, Bertsch U, Salwender H, Zweegman S, Vellenga E, Broyl A, Blau IW, Weisel KC, Wittebol S, Bos GM, Stevens-Kroef M, Scheid C, Pfreundschuh M, Hose D, Jauch A, van der Velde H, Raymakers R, Schaafsma MR, Kersten MJ, van Marwijk-Kooy M, Duehrsen U, Lindemann W, Wijermans PW, Lokhorst HM, Goldschmidt HM
J Clin Oncol 2012 Aug 20;30(24):2946-55. Epub 2012 Jul 16 doi: 10.1200/JCO.2011.39.6820. PMID: 22802322
International staging system for multiple myeloma.
Greipp PR, San Miguel J, Durie BG, Crowley JJ, Barlogie B, Bladé J, Boccadoro M, Child JA, Avet-Loiseau H, Kyle RA, Lahuerta JJ, Ludwig H, Morgan G, Powles R, Shimizu K, Shustik C, Sonneveld P, Tosi P, Turesson I, Westin J
J Clin Oncol 2005 May 20;23(15):3412-20. Epub 2005 Apr 4 doi: 10.1200/JCO.2005.04.242. PMID: 15809451

Recent systematic reviews

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.
Li Q, Ai L, Zuo L, Li J, Zhao F, Xu A, Zhang B, Cai L, Hu Y, Sun C
Ann Med 2024 Dec;56(1):2338604. Epub 2024 Apr 10 doi: 10.1080/07853890.2024.2338604. PMID: 38599340Free PMC Article
Treatment benefit of upfront autologous stem cell transplantation for newly diagnosed multiple myeloma: a systematic review and meta-analysis.
Lin CM, Chang LC, Shau WY, Chen CL, Yao CY, Tien FM
BMC Cancer 2023 May 16;23(1):446. doi: 10.1186/s12885-023-10907-1. PMID: 37193978Free PMC Article
Is RDW a clinically relevant prognostic factor for newly diagnosed multiple myeloma? A systematic review and meta-analysis.
Chen X, Liu J, Duan J, Xiong H, Liu Y, Zhang X, Huang C
BMC Cancer 2022 Jul 19;22(1):796. doi: 10.1186/s12885-022-09902-9. PMID: 35854269Free PMC Article

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