21.2. Solitary plasmacytoma of bone

Chapter 21

SPB represents 3 - 5% of plasma cell neoplasms and is approximately twice as common in men as in women [469]. The majority (83%) of tumours occur in the axial skeleton, particularly the vertebrae [469]. An example of a tumour affecting the mandible is presented in Figure 21.1. The diagnostic criteria for SPB are listed below.

Criteria for the diagnosis of solitary plasmacytoma of bone [471]

▪ Low concentration or absence of monoclonal protein in serum and/or urine

▪ Single area of bone destruction due to clonal plasma cells

▪ Bone marrow not consistent with MM

▪ Normal skeletal survey (and magnetic resonance imaging [MRI] of spine and pelvis if performed)

▪ No related organ or tissue impairment (no end organ damage other than a solitary bone lesion)

The outcome for patients with SPB is varied. Progression to MM is most frequent and has been reported to occur in approximately 50% of patients, with a median time to progression of 21 months. In 13% of patients, recurrence of the disease occurs at the site of the original lesion [472] but some patients develop new bone lesions with normal intervening bone marrow, consistent with a ‘macrofocal’ pattern of growth [473] Other patients may remain clinically stable for more than a decade [473]. The 10-year disease free survival for SPB is reported to be between 25 and 46% and the median overall survival between 7 and 12 years [474].

21.2.1. Monoclonal proteins in patients with solitary plasmacytoma of bone

From a review of seven different studies, it was reported that immunofixation electrophoresis (IFE) of serum and/or concentrated urine identified a small monoclonal protein in between 24 - 72% of patients with SPB [473]. When present, a monoclonal protein can be useful for guiding therapy. In most patients, the monoclonal protein is markedly reduced upon completion of local radiotherapy but it only disappears entirely in a minority of patients. Persistence of the monoclonal protein may indicate the presence of a tumour outside the field of radiotherapy [473]. The potential utility of sFLC analysis has been investigated in a growing number of studies, the most comprehensive of which was performed retrospectively by Dingli et al. [472] at the Mayo Clinic. Of 116 patients with a serum sample taken at diagnosis and prior to any therapy, the κ/λ sFLC ratio was abnormal in 54 (47%). Three smaller studies have reported abnormal κ/λ sFLC ratios in 30 - 68% of patients at diagnosis [475][476].

21.2.2. Prognostic factors in patients with solitary plasmacytoma of bone

Many attempts have been made to identify prognostic factors associated with disease-free survival and progression to MM. Tumour location, presence of a monoclonal protein at diagnosis [478], persistence of a serum monoclonal protein [479] and low levels of uninvolved immunoglobulins [480] have each been reported to be associated with progression. However, the relatively small number of patients studied has limited the ability to draw robust conclusions [481]; moreover, the prognostic utility of many factors has not been consistent between series. One of the more reliable predictors of progression is the persistence of a serum monoclonal protein [472][479]. However, as this can only be assessed at 1 or 2 years following therapy, there is a clear need for reliable prognostic markers that can be measured at diagnosis [472].

The prognostic utility of baseline sFLC measurements was evaluated by Dingli et al. [472]. A total of 43/116 patients progressed to MM with a median time to progression of 1.8 years. An abnormal κ/λ sFLC ratio was associated with a 44% risk of progression at 5 years compared with a 26% risk in patients with a normal κ/λ sFLC ratio (p=0.039) (Figure 21.2). Patients with an abnormal κ/λ sFLC ratio also had a shorter overall survival (Figure 21.3). At 1 - 2 years after therapy, a persistent serum monoclonal immunoglobulin concentration of ≥5 g/L was an additional risk factor for progression to MM. A risk stratification model was therefore constructed based on these two risk factors (an abnormal κ/λ sFLC ratio at baseline and a monoclonal protein concentration of >5 g/L at 1 - 2 years following diagnosis). Low-, intermediate- and high-risk groups of progression to MM corresponded to none, one or two risk factors, and these gave 5-year progression rates of 13%, 26% and 62% respectively (Figure 21.4). The authors commented that sFLC analysis provided an important prognostic indicator in these patients.

Subsequent studies have further highlighted the prognostic potential of sFLC analysis. Koch et al. [475] reported that 17/32 (53%) patients with an abnormal sFLC ratio at diagnosis progressed to MM compared with 2/17 (12%) patients with a normal κ/λ sFLC ratio at diagnosis. The authors concluded that an abnormal baseline κ/λ sFLC ratio was significantly associated with progression to MM (p=0.012). Most recently, Fouquet and colleagues [476] proposed a risk stratification model that incorporates an abnormal involved FLC (iFLC) concentration and whole body, fluorodeoxyglucose positron emission tomography – computed tomography (FDG-PET CT) at diagnosis. This model was constructed using patients with both bone and extramedullary plasmacytomas and is discussed in detail in Section 21.3.

In summary, these reports indicate that baseline sFLC abnormalities are consistently associated with increased risk of progression from SPB to MM, and sFLC analysis is recommended in IMWG guidelines for all patients with solitary plasmacytoma (Section 25.3.1).

21.2.3. Monitoring solitary plasmacytoma of bone using sFLCs

There is some data to support the use of sFLC analysis to monitor patients with SBP. Leleu et al. [483] monitored 10 patients and observed a trend to shorter time to progression (to MM) in patients with no change in sFLCs following radiotherapy. The same group [484] also described a patient with monoclonal κFLC in whom sFLCs were abnormal at disease relapse while electrophoresis and MRI were both ‘unremarkable’. A subsequent MRI investigation and biopsy confirmed relapse 6 months later, whilst serum and urine electrophoresis results remained normal.

National Comprehensive Cancer Network® (NCCN®) guidelines recommened sFLC analysis alongside serum protein electrophoresis (SPE) and serum IFE in a panel of tests for surveillance/follow-up of solitary plasmacytoma after primary treatment (Section 25.8) [485].