Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria

Abstract

In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. The median time to progression (TTP) was 57 months (CI, 45–72). BMPC% > 20% [hazard ratio (HR): 2.28 (CI, 1.63–3.20); p < 0.0001]; M-protein > 2g/dL [HR: 1.56 (CI, 1.11–2.20); p = 0.01], and FLCr > 20 [HR: 2.13 (CI, 1.55–2.93); p < 0.0001] independently predicted shorter TTP in multivariate analysis. Age and immunoparesis were not significant. We stratified patients into three groups: low risk (none of the three risk factors; n = 143); intermediate risk (one of the three risk factors; n = 121); and high risk (≥2 of the three risk factors; n = 153). The median TTP for low-, intermediate-, and high-risk groups were 110, 68, and 29 months, respectively (p < 0.0001). BMPC% > 20%, M-protein > 2 g/dL, and FLCr > 20 at diagnosis can be used to risk stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression.

Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management

“…There are several investigational approaches that are promising and patients should be considered for clinical trials investigating these approaches. Two of the most exciting options include antigen receptor T cells (CAR‐T) targeting B cell maturation antigen (BCMA) such as bb2121, 159 and belantamab mafodotin (a humanized anti‐BCMA antibody that is conjugated to monomethyl auristatin‐F, a microtubule disrupting agent) 160 . Another option that is promising is the use of a bispecific T cell engager, such as AMG 701.…”

Cytogenetic subclone formation and evolution in progressive smoldering multiple myeloma

“…Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM) consistently precede symptomatic Multiple Myeloma (MM) requiring systemic therapy [1]. Several factors have been identified to predict higher risk of progression in asymptomatic patients [2]. High-risk chromosomal aberrations (CA) are associated with an increased risk of progression into symptomatic myeloma [2][3][4].…”

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies

“…M-protein >2g/dL (hazard ratio (HR) 1.56, p = 0.01; BMPC % >20% (HR 2.28, p < 0.0001), and FLC ratio (FLCr) >20 (HR 2.13, p < 0.0001)) independently predicted shorter time to progression (TTP) in multivariate analysis. Three risk groups were identified: Low risk (none of the risk factors), intermediate risk (1 risk factor), and high risk (≥2 risk factors), with a median TTP of 110, 68, and 29 months, respectively (p < 0.0001) [45]. The high-risk group consisted of 36% of the analyzed cohort of SMM.…”