Outcome prediction in plasmacytoma of bone: a risk model utilizing bone marrow flow cytometry and light-chain analysis

Abstract

Key Points• Occult marrow disease is demonstrable in 68% of patients with solitary plasmacytoma of bone and is predictive of progression.• Trials of adjuvant systemic therapy are warranted in high-risk patients.The purpose of this study was to use multiparameter flow cytometry to detect occult marrow disease (OMD) in patients with solitary plasmacytoma of bone and assess its value in predicting outcome. Aberrant phenotype plasma cells were demonstrable in 34 of 50 (68%) patients and comprised a median of 0.52% of bone marrow leukocytes. With a median follow-up of 3.7 years, 28 of 50 patients have progressed with a median time to progression (TTP) of 18 months. Progression was documented in 72% of patients with OMD vs 12.5% without (median TTP, 26 months vs not reached; P 5 .003). Monoclonal urinary light chains (ULC) were similarly predictive of outcome because progression was documented in 91% vs 44% without (median TTP, 16 vs 82 months; P < .001). By using both parameters, it was possible to define patients with an excellent outcome (lacking both OMD and ULC, 7.7% progression) and high-risk patients (OMD and/or ULC, 75% progression; P 5 .001). Trials of systemic therapy are warranted in high-risk patients. (Blood. 2014;124(8):1296-1299 IntroductionSolitary plasmacytoma of bone (SPB) is characterized by localized areas of bone destruction by monoclonal plasma cells in the absence of clinical, laboratory, and radiologic features of multiple myeloma (MM). 1 Local irradiation remains the treatment of choice. United Kingdom national guidelines recommend doses of 40 to 50 Gy depending on tumor size, with a 2-cm margin, because this provides excellent local control.2 A significant proportion of patients will however progress with new lesions outside the irradiation field or, more typically, with generalized myeloma. The overall incidence of progression is 37% to 72%, with median reported times to progression (TTP) of 2 years or less. [3][4][5][6][7][8][9][10] We hypothesized that progression in SPB might occur as a result of occult disease outside of the irradiation field. To further evaluate this, we used multiparameter flow cytometry (MFC) to assess staging bone marrow (BM) samples for the presence of occult disease and determine its impact on outcome. Patients and methodsFifty patients (median age, 65years) with a histologically confirmed diagnosis of SPB according to International Myeloma Working Group (IMWG) criteria 1 were evaluated between 1998 and 2008. The solitary nature of the presenting lesion was confirmed by plain radiography in all patients, and 35 also had negative spinal magnetic resonance imaging results. Positron emission tomography (PET) scanning was not routinely performed. Thirty-five of 50 patients had a monoclonal protein (27 IgG, 7 IgA, and 1 light-chain only) with a median concentration of 7 g/L. Urine immunofixation demonstrated monoclonal urinary light chains (ULC) in 11 of 45 patients, but the serum-free light-chain (SFLC) assay was not routinely available. Patients were treated in two r...

Progression of a solitary plasmacytoma to multiple myeloma. A population‐based registry of the northern Netherlands

“…The presence of this occult bone marrow disease (OMD) is of prognostic significance and is highly predictive for progression to MM, with a time to progression of 18–26 months. (Hill et al , ; Pavia et al , ). The strong predictive value of OMD and the short PFS supports the potential use of systemic treatment in addition to local radiotherapy in this high‐risk group of SBP.…”

Radiotherapy Alone is Associated with Improved Outcomes Over Surgery in the Management of Solitary Plasmacytoma

“…Thus, we believe dose escalation is only potentially beneficial, requiring for evidence from well-designed studies. On the other hand, risk factors for MM are: serum β2 microglobulin≥3.5 mg/L (Guo et al, 2013), bone invasion (Ozsahin et al, 2006), involvement of axial bone (Bataille et al, 1981), age (Tournier-Rangeard et al, 2006), monoclonal urinary light chains (Hill et al, 2014) and positive multiparameter flow cytometry (Paiva et al, 2014). Reported by Huang et al, in patients with SP of cervical spine, adjunctive RT following excision obviously decreased MM progression (Huang et al, 2010).…”

International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma

“…The prognosis of solitary plasmacytoma varies depending on presence of clonal plasma cells in the bone marrow. [12][13][14][15][16] It therefore consists of two distinct entities: solitary plasmacytoma (no clonal BMPCs) and solitary plasmacytoma with low marrow involvement (<10% clonal BMPCs). By contrast, patients with solitary plasmacytoma and 10% or more of clonal plasma cells are classifi ed as multiple myeloma.…”

“…[5][6][7][8][9] The diagnosis of MGUS requires the absence of hypercalcaemia, renal failure, anaemia, and bone lesions (referred to as CRAB features) that can be attributed to the underlying plasma cell disorder (all features must be absent; table 1). [10][11][12][13][14][15][16][17][18][19][20] About 80% of multiple myeloma originates from non-IgM immunoglobulin MGUS (nonIgM MGUS), and 20% from light-chain immunoglobulin MGUS (LC-MGUS). In the event of progression, IgM immunoglobulin MGUS (IgM MGUS) usually evolves into Waldenström macroglobulinaemia, but in rare instances IgM MGUS can progress to multiple myeloma (IgM myeloma).…”