Smoldering multiple myeloma risk factors for progression: a Danish population‐based cohort study

Abstract

Several risk scores for disease progression in patients with smoldering multiple myeloma (SMM) have been proposed; however, all have been developed using single-center registries. To examine risk factors for time to progression (TTP) to multiple myeloma (MM) for SMM, we analyzed a nationwide population-based cohort of 321 patients with newly diagnosed SMM registered within the Danish Multiple Myeloma Registry between 2005 and 2014. Significant univariable risk factors for TTP were selected for multivariable Cox regression analyses. We found that both an M-protein ≥30 g/L and immunoparesis significantly influenced TTP (HR 2.7, 95%CI (1.5;4.7), P = 0.001, and HR 3.3, 95%CI (1.4;7.8), P = 0.002, respectively). High free light chain (FLC) ratio did not significantly influence TTP in our cohort. Therefore, our data do not support recent IMWG proposal of identifying patients with FLC ratio above 100 as having ultra high-risk of transformation to MM. Using only immunoparesis and M-protein ≥30 g/L, we created a scoring system to identify low-, intermediate-, and high-risk SMM. This first population-based study of patients with SMM confirms that an M-protein ≥30 g/L and immunoparesis remain important risk factors for progression to MM.

Risk factors for infections in newly diagnosed Multiple Myeloma patients: A Danish retrospective nationwide cohort study

“…Complete follow‐up was available for all but one patient (n = 2557). The registry contains information on baseline biochemistry, treatment regimens, and response to treatment as described previously . Cyclophosphamide‐dexamethasone (CyDex)‐based induction regimens were mainly used in the calendar period 2005‐2008 before ASCT, and this regime was in the calendar period 2009‐2013 changed to bortezomib‐dexamethasone (VD)‐based induction regimens alone or in combination with cyclophosphamide (VCD).…”

“…The registry contains information on baseline biochemistry, treatment regimens, and response to treatment as described previously. 22 Immunoglobulin substitution therapy, pneumococcal vaccination, or antibiotic prophylaxis were not routinely used for Danish MM patients during the study period. 23 Qualitative immunoparesis was defined as one or more of uninvolved immunoglobulins below the normal levels IgG <6.1 g/L, IgA <0.70 g/L and/or IgM <0.39 g/L at time of diagnosis.…”

Bone marrow Dikkopf‐1 levels are a new independent risk factor for progression in patients with smouldering myeloma

“…Serum free light chain (FLC) levels and FLC ratio were not available in all patients and consequently we did not find a statistically significant relationship with progression. However, two recent studies (Waxman et al , ; Sorrig et al , ) observed that an abnormal FLC ratio is not considerable as a stand‐alone high risk factor for progression to active MM in SMM patients.…”

Diagnosis, risk stratification and management of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma

“…Treatment should be considered in these patients to prevent serious end-organ damage such as bone fractures or renal failure, which can have longterm effects on the quality of life of patients. However, two recent studies showed that SMM patients with a FLC ratio ≥100 have a 2-year progression risk of 30% and 64% [19,20], which is lower than reported in two previous studies (progression risk at 2 years:~80%) [21,22] that were used for these updated IMWG criteria [18]. The authors from these studies conclude that FLC ratio ≥100 as a sole criterion for treating as active MM may not be justified, but that very close monitoring is warranted for this group.…”

“…Several other prognostic models have been published, including a recent Danish model derived from a population-based study, in which M-protein ≥30 g/ L and immunoparesis were markers for time to progression to MM in SMM (Table 3) [20]. In addition, the Arkansas group generated a risk-stratification model based on expression levels of only four genes combined with serum M-protein (≥30 g/L) and albumin levels (<35 g/L).…”