Demonstration of changes in plasma cell subsets in multiple myeloma

Ayliffe, M. J.; Davies, Faith E.; Castro, David; Morgan, Gareth J.

doi:10.3324/haematol.11133

Cited by 26 publications

(23 citation statements)

References 9 publications

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“…Monitoring for the type of immunoglobulin produced and secreted at relapse (either a whole immunoglobulin or just a light chain) provides an excellent tool to study the global impact of intraclonal heterogeneity. The basic premise in this model is that patients harbor different clones with different secretory behavior, 14 that is, 1 clone is able to produce a complete antibody, whereas the other secretes only an FLC and this can be used as a marker for subclonal progression. There is great heterogeneity in the patterns of monoclonal immunoglobulin types and levels secreted by the myeloma clones of different patients at presentation, before therapy has been administered.…”

Section: Discussionmentioning

confidence: 99%

“…8 In recent years, in addition to the assessment of paraprotein levels in serum and urine, the diagnostic workup of MM has seen the introduction of serum FLC assays that can also be routinely used to both diagnose and monitor changes in disease activity. [9][10][11][12][13] We have provisionally noted subclonal differences in heavy and light chain production within the predominant myeloma clones 14 and, as such, the type of immunoglobulin produced can provide an excellent marker of clonal change over time. To better understand the extent of subclonal evolution over time as well as its impact on outcomes following relapse, we have prospectively evaluated serial FLC and paraprotein measurements in a large population of newly diagnosed MM patients treated within the Myeloma IX clinical trial.…”

Section: Introductionmentioning

confidence: 99%

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Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome

Brioli

Giles

Pawlyn

et al. 2014

Blood

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Key Points• The type of antibody secreted at relapse can serve as a marker of clonal heterogeneity.• It is important to monitor for serum FLC in the suspicion of clinical relapse to ensure that FLC relapse is not missed.Intraclonal heterogeneity was recently described in multiple myeloma (MM), but its full impact on disease progression and relapse has not been entirely explored. The immunoglobulin type produced by myeloma cells provides an excellent marker to follow changes in clonal substructure over time. We have prospectively evaluated serial paraprotein and serum free light chain (FLC) measurements and found that 258 of 520 and 54 of 520 patients who presented with a whole paraprotein relapsed with paraprotein only (PO) and "FLC escape," respectively. The median overall survival of PO patients was longer, when compared with patients whose relapse manifested as an increase in FLC both alone and with a whole paraprotein, as a result of a significantly shorter survival from relapse of the latter groups. These observations fit a model in which 1 clone is able to produce a complete antibody, whereas the other secretes only FLC; the type of relapse represents the outgrowth of different clones, some of which are more resistant to therapy. To our knowledge, this is the largest series describing patients who have relapsed with FLC escape and highlights the importance of monitoring FLC when there is a suspicion of clinical relapse. This study was registered at www.isrctn. org as ISRCTN68454111. (Blood. 2014;123(22):3414-3419)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome

Brioli

Giles

Pawlyn

et al. 2014

Blood

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“…A significant minority of myeloma patients (18%) have two populations of plasma cells, one population expressing intact immunoglobulin and the other light chain only and these patients have a shorter survival (Ayliffe et al, 2007). During the course of their disease some patients showed a progression from having tumour cells expressing intact immunoglobulin to a population of tumour cells expressing light chain only (Ayliffe et al, 2007).…”

Section: Review ª 2008 the Authormentioning

confidence: 99%

“…With the advent of newer agents and reduced intensity allogeneic transplantation novel manifestations of relapse with extramedullary disease and free light chain breakthrough appear more frequent (Dawson et al, 2007). A significant minority of myeloma patients (18%) have two populations of plasma cells, one population expressing intact immunoglobulin and the other light chain only and these patients have a shorter survival (Ayliffe et al, 2007). During the course of their disease some patients showed a progression from having tumour cells expressing intact immunoglobulin to a population of tumour cells expressing light chain only (Ayliffe et al, 2007).…”

Section: Review ª 2008 the Authormentioning

confidence: 99%

The evolving use of serum free light chain assays in haematology

Pratt

2008

Br J Haematol

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SummaryOver the last few years new immunoassays have emerged that allow the measurement of free immunoglobulin light chains (FLCs) in serum to a level of 2–4 mg/l and provide a much greater sensitivity than older methods, such as immunofixation, which is able to detect FLCs at a minimum concentration of 100–150 mg/l. The new FLC assay has enabled the detection of monoclonal protein in some patients with non‐secretory myeloma and amyloidosis that were previously undetectable. FLC measurements are quantitative, correlating with disease activity, and are an advance in monitoring light chain only multiple myeloma, AL amyloidosis, non‐secretory and oligo‐secretory multiple myeloma. Serum FLC concentrations also reflect the disease course in the majority of myeloma patients producing intact monoclonal immunoglobulin proteins and have been incorporated into the new response criteria. The rapid half life of λ and κ free light chains means that FLC assays may provide a more rapid indication of the response to treatment but their clinical utility in this setting needs further study. An abnormal FLC ratio has been shown to be a risk factor for progression of monoclonal gammopathy of undetermined significance, smouldering myeloma and solitary plasmacytoma of bone and is prognostic in multiple myeloma.

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“…Although local response to radiotherapy is very good [7][8][9][10] , about half of patients with SPs eventually develop a multiple myeloma [11][12][13][14][15][16][17] . Prescription doses used to irradiate this type of tumors are discussed in the literature.…”

Section: Discussionmentioning

confidence: 99%

Helical tomotherapy and systemic targeted therapies in solitary plasmacytoma: Pilot study

Wiazzane

Chargari²,

Plancher³

et al. 2013

WJR

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AIM:To assess the feasibility of the combination of helical tomotherapy ® (HT) and a concurrent systemic targeted therapy in patients with solitary plasmacytoma (SP) with the aim to decrease toxicity while improving therapeutic efficacy. METHODS:Six patients with biologically, histologically, and radiologically confirmed SP were treated using HT and a systemic targeted treatment concomitantly. Total dose was 40 Gy/20 fractions. Four patients received 4 cycles of concurrent lenalidomide-dexamethasone combination and two patients were treated with concomitant bortezomib-dexamethasone. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0. RESULTS:Five patients had a bone tumor and one patient had an isolated pancreatic mass. Five patients presented with pain, one had neurologic symptoms related to medullary compression, which was treated by an emergency surgery. Median age was 59.5 years (range, 50-74 years). All patients had initial positron emission tomography-computed tomographys, three patients had total body bone magnetic resonance imaging examination, and three patients had computed tomodensitometry scans. The toxicity profile was excellent with no higher than grade 1 toxicity. Four of the six patients experienced a partial radiological response, four had complete response on positions emission tomography and 5/6 patients experienced a complete relief of their symptoms 4 mo after treatment. At a median follow-up of 18 mo, 5/6 patients were controlled clinically, radiologically, and biologically.CONCLUSION: Using HT, we could deliver a highly conformal irradiation concurrently with a molecularly targeted therapy. This association yielded in a high response rate and a low toxicity. A prospective study with longer follow-up will help determining the true benefit of such strategy.

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Demonstration of changes in plasma cell subsets in multiple myeloma

Cited by 26 publications

References 9 publications

Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome

Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome

The evolving use of serum free light chain assays in haematology

Helical tomotherapy and systemic targeted therapies in solitary plasmacytoma: Pilot study

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