Chapter 2 – Diagnosis and staging

Contributors: Carlos Fernández de Larrea and Joan Bladé


1 Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111:2962-2972.
2 Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15:e538-548.
3 Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21-33.
4 Fernández de Larrea C, Delforge M, Davies F, Bladé J. Response evaluation and monitoring of multiple myeloma. Expert Rev Hematol. 2014;7:33-42.
5 Landgren O, Kyle RA, Pfeiffer RM, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113:5412-5417.
6 Kyle RA, Durie BG, Rajkumar SV, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24:1121-1127.

7 Korde N, Kristinsson SY, landgren O. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies. Blood. 2011;117:5573-5581.
8 Bladé J. Clinical practice. Monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;355:2765-2770.
9 Kyle RA, Therneau TM, Rajkumar SV, et al. Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood. 2003;102:3759-3764.
10 Bladé J, Dimopoulos M, Rosiñol l, Rajkumar SV, Kyle RA. Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J Clin Oncol. 2010;28:690-697.
11 Mateos MV, González-Calle V. Smoldering Multiple Myeloma: Who and When to Treat. Clin Lymphoma Myeloma Leuk. 2017;17:716-722.
12 Pérez-Persona E, Vidriales MB, Mateo G, et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 2007;110:2586-92.
13 Kyle RA, Remstein ED, Therneau TM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007;356:2582-90.
14 Fernández de Larrea C, Kyle RA, Durie BG, et al. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia. 2013;27:780-791.
15 Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122-1128.
16 Dimopoulos MA, Terpos E, Chanan-Khan A, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010;28:4976-4984.
17 Fonseca R, Bergsagel PL, Drach J, et al. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009;23:2210-2221.
18 Moreau P, Cavo M, Sonneveld P, et al. Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related death. J Clin Oncol. 2014;32:2173-2180.
19 Avet-Loiseau H, Durie BG, Cavo M, et al. Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project. Leukemia. 2013;27:711-717.
20 Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36:842-854.
21 Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23:3412-3420.
22 Palumbo A, Avet-Loiseau H, Oliva S, et al. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015;33:2863-2869.
23 Dimopoulos M, Terpos E, Comenzo RL, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia. 2009;23:1545-1556.
24 Brioli A, Morgan GJ, Durie B, Zamagni E. The utility of newer imaging techniques as predictors of clinical outcomes in multiple myeloma. Expert Rev Hematol. 2014;7:13-16.
25 Cavo M, Terpos E, Nanni C, et al. Role of ¹⁸F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group. Lancet Oncol 2017;18:e206-217.
26 Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102:1115-1123.
27 Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20:1467-1473.
28 Tovar N, de Larrea CF, Aróstegui JI, et al. Natural history and prognostic impact of oligoclonal humoral response in patients with multiple myeloma after autologous stem cell transplantation: long-term results from a single institution. Haematologica. 2013;98:1142-1146.
29 Martinez-Lopez J, Blade J, Mateos MV, et al. Long-term prognostic significance of response in multiple myeloma after stem cell transplantation. Blood. 2011;118:529-534.
30 Harousseau JL, Avet-Loiseau H. Minimal Residual Disease Negativity Is a New End Point of Myeloma Therapy. J Clin Oncol. 2017;35:2863-2865.
31 Paiva B, Gutiérrez NC, Rosiñol L, et al. High-risk cytogenetics and persistent minimal residual disease by multiparameter flow cytometry predict unsustained complete response after autologous stem cell transplantation in multiple myeloma. Blood. 2012;119:687-691.
32 Lahuerta J-J, Paiva B, Vidriales M-B, et al. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials. J Clin Oncol. 2017;35:2900-2910.
33 Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016;17:e328-346.
34 Paiva B, Almeida J, Pérez-Andrés M, et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom. 2010;78:239-252.
35 Paiva B, Vidriales MB, Cerveró J, et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood. 2008;112:4017-4023.
36 Paiva B, Martinez-Lopez J, Vidriales MB, et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol. 2011;29:1627-1633.
37 Mailankody S, Korde N, Lesokhin AM, et al. Minimal residual disease in multiple myeloma: bringing the bench to the bedside. Nat Rev Clin Oncol. 2015;12:286-295.
38 Ladetto M, Pagliano G, Ferrero S, et al. Major tumor shrinking and persistent molecular remissions after consolidation with bortezomib, thalidomide, and dexamethasone in patients with autografted myeloma. J Clin Oncol. 2010;28:2077-2084.
39 Puig N, Sarasquete ME, Balanzategui A, et al. Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiple myeloma. A comparative analysis with flow cytometry. Leukemia. 2014;28:391-397.
40 Kapoor P, Kkumar SK, Dispenzieri A, et al. Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma. J Clin Oncol. 2013;31:4529-4535.
41 Martinez-Lopez J, Lahuerta JJ, Pepin F, et al. Prognostic value of deep sequencing method for minimal residual disease detection in multiple myeloma. Blood. 2014;123:3073-3079.
42 Zamagni E, Nanni C, Mancuso K, et al. PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma. Clin Cancer Res. 2015;21:4384-4390.
43 Beksac M, Gunduz M, Ozen M, et al. Impact of PET-CT Response on Survival Parameters Following Autologous Stem Cell Transplantation Among Patients with Multiple Myeloma: Comparison of Two Cut-Off Values. Blood 2014;124:3983.