Although novel treatment strategies have resulted in improved outcomes (including response rates and survival), MM remains an incurable disease. Patients with MM will inevitably relapse.
The major causes of death are infections, disease progression, and renal failure.
Surveillance, Epidemiology, and End Results (SEER) Program data report the following 5-year relative survival rates for patients diagnosed with myeloma (2014-2020 data):[219]National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER Explorer: myeloma SEER 5-year relative survival rates, 2014-2020.
https://seer.cancer.gov/statistics-network/explorer/application.html
The International Staging System (ISS) criteria is a validated tool used to categorize patients with MM into one of the following three prognosis groups based on serum beta2-microglobulin and serum albumin levels:[61]Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005 May 20;23(15):3412-20.
https://ascopubs.org/doi/10.1200/JCO.2005.04.242
http://www.ncbi.nlm.nih.gov/pubmed/15809451?tool=bestpractice.com
[63]D'Agostino M, Cairns DA, Lahuerta JJ, 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. 2022 Oct 10;40(29):3406-18.
https://ascopubs.org/doi/10.1200/JCO.21.02614?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/35605179?tool=bestpractice.com
Stage I: beta2-microglobulin <3.5 mg/L and albumin ≥3.5 g/dL; these patients have a median survival of 62 months
Stage II: not stage I or III; these patients have a median survival of 44 months
Stage III: beta2-microglobulin ≥5.5 mg/L; these patients have a median survival of 29 months
Revised versions of the ISS (RISS and R2-ISS) incorporate chromosomal abnormalities and serum lactate dehydrogenase as additional parameters to improve risk stratification and prognostication.[62]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 Sep 10;33(26):2863-9.
https://ascopubs.org/doi/10.1200/JCO.2015.61.2267
http://www.ncbi.nlm.nih.gov/pubmed/26240224?tool=bestpractice.com
[63]D'Agostino M, Cairns DA, Lahuerta JJ, 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. 2022 Oct 10;40(29):3406-18.
https://ascopubs.org/doi/10.1200/JCO.21.02614?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/35605179?tool=bestpractice.com
See Criteria.
Treatment response criteria
The International Myeloma Working Group has developed uniform response criteria for treatment efficacy, which can also help with prognostic stratification. According to these criteria, complete response is defined by the absence of serum and urine monoclonal protein by immunofixation or electrophoresis, absence of any soft-tissue plasmacytomas, and less than 5% plasma cells in the bone marrow.[220]Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006 Sep;20(9):1467-73.
http://www.ncbi.nlm.nih.gov/pubmed/16855634?tool=bestpractice.com
Minimal residual disease (MRD)-negative status (i.e., absence of MRD) has been added to the criteria for complete response in order to further stratify the criteria due to the high frequency of recurrence among complete responders as previously defined, and with the availability of newer treatments with high response rates.[216]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 Aug;17(8):e328-46.
http://www.ncbi.nlm.nih.gov/pubmed/27511158?tool=bestpractice.com
Two meta-analyses found that MRD-negative status after treatment for newly diagnosed MM is associated with prolonged overall survival.[221]Munshi NC, Avet-Loiseau H, Rawstron AC, et al. Association of minimal residual disease with superior survival outcomes in patients with multiple myeloma: a meta-analysis. JAMA Oncol. 2017 Jan 1;3(1):28-35.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2552677
http://www.ncbi.nlm.nih.gov/pubmed/27632282?tool=bestpractice.com
[222]Landgren O, Devlin S, Boulad M, et al. Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis. Bone Marrow Transplant. 2016 Dec;51(12):1565-8.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571752
http://www.ncbi.nlm.nih.gov/pubmed/27595280?tool=bestpractice.com
Sustained MRD, which is two consecutive MRD results of 10⁻⁵ 12 months apart, represents an additional MRD criterion.[216]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 Aug;17(8):e328-46.
http://www.ncbi.nlm.nih.gov/pubmed/27511158?tool=bestpractice.com
The prognostic impact of sustained MRD is likely superior to that of a one-time MRD assessment and continues to be explored as part of clinical trials.[223]San-Miguel J, Avet-Loiseau H, Paiva B, et al. Sustained minimal residual disease negativity in newly diagnosed multiple myeloma and the impact of daratumumab in MAIA and ALCYONE. Blood. 2022 Jan 27;139(4):492-501.
https://ashpublications.org/blood/article/139/4/492/476415/Sustained-minimal-residual-disease-negativity-in
http://www.ncbi.nlm.nih.gov/pubmed/34269818?tool=bestpractice.com
MRD status can be evaluated by next-generation flow cytometry or next-generation DNA sequencing with varying levels of sensitivity. Although MRD status is emerging as a strong prognostic marker, further study is required to determine its role in clinical decision making.