scholarly journals Monoclonal Gammopathy of Ocular Significance (MGOS) - a Series of Corneal Manifestations and Treatment Outcomes

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2695-2695
Author(s):  
Laurent Garderet ◽  
Mohammad Al Hariri ◽  
Joanna Wasielica-Poslednik ◽  
Markus Munder ◽  
Kitti Kormányos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Systemic Therapy ◽  
Monoclonal Gammopathy ◽  
Management Strategies ◽  
Health Assessment ◽  
Unknown Origin ◽  
Initial Response ◽  
Patient Characteristics ◽  
Response To Treatment ◽  
Plasma Cell Dyscrasia

Abstract Introduction Monoclonal gammopathy of ocular significance (MGOS) is a rare subset of monoclonal gammopathy of clinical significance (MGCS) occurring secondary to plasma cell dyscrasia resulting in ocular manifestations. Given the rarity of these conditions, optimal management strategies are not defined; the approach is dependent upon the underlying cause of the monoclonal gammopathy and whether or not the patient's vision is affected. We report our review of 23 cases with MGOS, more specifically on paraproteinemic keratopathy (PPK) the most common form, to obtain a better understanding of the patient characteristics, diagnosis and treatments. Methods We report an international retrospective series of patients with MGOS. Data was collected on patients with MGOS:there were no other inclusion criteria besides monoclonal gammopathy with an ophthalmologic manifestation; however, this report focuses only on patients with PPK. Efficacy outcomes were the hematologic and the ocular responses in patients with PPK. Hematologic responses were reported according to the IMWG response criteria. The ophthalmologic response to treatment was assessed by each contributing physician and reported as either complete, partial or no sight recovery. Results We identified 23 patients with PPK in the setting of monoclonal gammopathy of unknown significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM) diagnosed between 2006 and 2019 in 7 countries. Table 1 summarizes the patients' characteristics. The ocular diagnosis was typically made at the same time or after the hematologic diagnosis. Eleven of 23 patients presented decreased vision. Four were treated by penetrating keratoplasty with or without systemic therapy, including chemotherapy with new generation anti-MM agents with or without autologous stem cell transplantation (ASCT). All patients with MM and 40% of those with other diagnoses such as SMM or MGUS received systemic therapy. In most cases, neither ocular nor hematologic treatment, even when ASCT was performed, afforded a durable improvement in the visual acuity despite initial responses. MGOS typically relapsed within one year of the initial response (Table 2). Conclusion To date, this is the largest retrospective study focusing on MGOS patients with monoclonal immunoglobulin deposits accumulating in the cornea and resulting in visual impairment. Further studies will be required to determine the optimal strategy to treat and prevent the relapse of ocular symptoms in patients with PPK and specifically to address the timing of keratoplasty and systemic chemotherapy and the role of maintenance therapy. Patients with corneal manifestation of unknown origin should undergo a hematologic check-up and patients with paraproteinemia should have a periodic ocular health assessment. Figure 1 Figure 1. Disclosures Garderet: Takeda: Consultancy; Sanofi: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Munder: Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy; Takeda: Consultancy, Honoraria; Amgen: Honoraria; Sanofi: Consultancy; GSK: Consultancy; Incyte: Research Funding. Gozzetti: AbbVie: Honoraria; Janssen: Honoraria. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Jurczyszyn: Janssen-Cilag, Amgen: Honoraria, Speakers Bureau.

scholarly journals A Comprehensive Review of the Genomics of Multiple Myeloma: Evolutionary Trajectories, Gene Expression Profiling, and Emerging Therapeutics

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1961
Author(s):  
Hassan Awada ◽  
Bicky Thapa ◽  
Hussein Awada ◽  
Jing Dong ◽  
Carmelo Gurnari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Expression Profiling ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Plasma Cell Dyscrasia ◽  
Genomic Evolution ◽  
Cytogenetic Aberrations ◽  
Evolutionary Trajectories ◽  
Prognostic Implications ◽  
Undetermined Significance

Multiple myeloma (MM) is a blood cancer characterized by the accumulation of malignant monoclonal plasma cells in the bone marrow. It develops through a series of premalignant plasma cell dyscrasia stages, most notable of which is the Monoclonal Gammopathy of Undetermined Significance (MGUS). Significant advances have been achieved in uncovering the genomic aberrancies underlying the pathogenesis of MGUS-MM. In this review, we discuss in-depth the genomic evolution of MM and focus on the prognostic implications of the accompanied molecular and cytogenetic aberrations. We also dive into the latest investigatory techniques used for the diagnoses and risk stratification of MM patients.

scholarly journals Monoclonal gammopathy of undetermined significance

Blood ◽  
2019 ◽  
Vol 133 (23) ◽  
pp. 2484-2494 ◽  
Author(s):  
Tarek H. Mouhieddine ◽  
Lachelle D. Weeks ◽  
Irene M. Ghobrial
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cell Clone ◽  
Plasma Cell Dyscrasia ◽  
Bone Marrow Niche ◽  
Immunologic Factors ◽  
Risk Of Progression ◽  
Undetermined Significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year. Recent advances have improved understanding of the complex genetic and immunologic factors that permit progression from the aberrant plasma cell clone to MGUS and overt MM. Additional evidence supports bidirectional interaction of MGUS cells with surrounding cells in the bone marrow niche that regulates malignant transformation. However, there are no robust prognostic biomarkers. Herein we review the current body of literature on the biology of MGUS and provide a rationale for the improved identification of high-risk MGUS patients who may be appropriate for novel clinical interventions to prevent progression or eradicate premalignant clones prior to the development of overt MM.

Multiclonality In Multiple Myeloma: A Retrospective Analysis Of Clonal Progression and Selection

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3147-3147
Author(s):  
Gwynivere Davies ◽  
Ian H. Chin-Yee
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Systemic Therapy ◽  
Partial Remission ◽  
M Protein ◽  
Treatment Modalities ◽  
Plasma Cell Dyscrasia ◽  
Inclusion Criteria ◽  
Over Time

Abstract Introduction Genomic instability and multiclonality is the hallmark of many cancers including multiple myeloma (MM). Genetic alterations and clonal prominence occur over time as patients undergo various treatment modalities and can be followed by examining factors such as copy number abnormalities. Occasionally more than one monoclonal spike is noted on the serum protein electrophoresis (SPEP) indicating the existence of several distinct populations of clonal plasma cells producing a measurable amount of monoclonal (M) protein. Using routinely measureable clinical assays, SPEP and serum free light chains (SFL), we set out to identify the prevalence of multiclonality in patients with plasma cell dyscrasia, and to examine the natural history and effect treatment practices have on clones over time. Methods We retrospectively identified adult patients who were registered with the London Regional Cancer Program (LRCP), a tertiary care referral center in London, Ontario, Canada, since 2000 with a diagnosis of monoclonal gammopathy of uncertain significance (MGUS), smoldering myeloma, multiple myeloma or solitary plasmacytoma. Our current SPEP quantitation method has been in use since September 2004, so these SPEP results of patients identified from our initial search were examined for evidence of multiple monoclonal peaks as a surrogate marker for multiclonality. Inclusion criteria required a new diagnosis of plasma cell dyscrasia since the year 2000 and biclonal/multiclonal M protein peaks on SPEP followed through the LRCP. Demographics, SPEP results, treatment modalities and last recorded follow up or death for these patients was recorded. Outcome measures included quantification of complete remission, partial remission, very good partial remission and no response following systemic therapy to look for concordance in clone response. Results Since 2000, 1402 patients met the inclusion criteria; 144 patients met our surrogate criteria for multiclonality, representing a prevalence of approximately 10%. The majority of patients had MGUS (58, 40.3%) or MM (70, 48.6%) at first identification. Of these patients, 96 (66.7%) were male and the average age at diagnosis was 65.9 years. 58 (40.3%), primarily with MGUS, had no treatment and thus cannot be examined for treatment selective pressures. The number of clones identified ranged from two (114, 79.2%) to five. 62 (43.1%) had clones that were of similar immunoglobulin and light chain subtype, and half of patients had multiple clones identified at the same time point compared with development of clones during follow up investigations. In order to examine for concordance in treatment response between clones, we required that clones have a pre- and post- treatment value and have received systemic therapy with a measurable nadir. Only 26 patients had values that met these criteria, mainly due to clones disappearing with time, including 7 patients with no treatment, or oral treatment without recurrence and thus not quantifiable for comparison. Of these 26, approximately half showed discordance between clones, even in those with clones of the same M protein subtype. Of note, 4 discordant patients initially showed the same response to treatment and later developed divergent responses. Discussion Multiclonality in plasma cell neoplasms is a common occurrence, with a prevalence of 10% in our patient population. The use of SPEP and SFL as surrogate markers for multiclonality likely underestimates the true prevalence of multiple clones measured by genetic methods due to insensitivity to resolved non secretory clones or multiple clones secreting similar immunoglobulin. As seen in previous studies, our results demonstrate that plasma cell clone response can diverge over time, potentially spontaneously or as a result of selection pressures imposed by therapy. These findings may help direct therapy and suggests prognosis as clonal divergence could herald genetic changes associated with therapy resistant disease. Disclosures: No relevant conflicts of interest to declare.

Consolidation and maintenance therapy in multiple myeloma: randomized comparison of a new approach to therapy after initial response to treatment.

1986 ◽  
Vol 4 (6) ◽  
pp. 888-899 ◽  
Author(s):  
H J Cohen ◽  
A A Bartolucci ◽  
W B Forman ◽  
H R Silberman
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Controlled Trial ◽  
Initial Response ◽  
Response To Treatment ◽  
Maximal Response ◽  
New Approach ◽  
Randomized Controlled ◽  
Alternative Approaches ◽  
The Impact

A randomized, controlled trial was initiated in 1977 to evaluate the impact of three alternative approaches to consolidation and maintenance therapy after initial maximal response for multiple myeloma. All patients were treated initially with BCNU, cyclophosphamide, and prednisone (BCP) until a designated level of response was achieved. Responders were randomly assigned to either melphalan and prednisone (MP); prednisone, Adriamycin (Adria Laboratories, Columbus, Ohio), azathioprine, and vincristine (PAIV), or no therapy until relapse, then treatment with BCP. Initial response rates were comparable with previous trials. A small number of incremental responses were observed with both MP and PAIV. Survival was the same for all three maintenance approaches and the same as that observed in our previous continuous BCP or MP therapy. Additional or consolidation/maintenance therapy of the type administered here appears to offer little advantage once an initial response has been achieved.

scholarly journals Plasma cell dyscrasia presenting as retro-orbital mass - lessons to learn?

2014 ◽  
Vol 2 (3) ◽  
pp. 158-160
Author(s):  
Srinivas Bacchu
Keyword(s):  
Renal Failure ◽  
Renal Impairment ◽  
Plasma Cell ◽  
Early Recognition ◽  
Initial Response ◽  
Response To Treatment ◽  
Plasma Cell Dyscrasia ◽  
Orbital Mass

A patient with myeloma presenting as retro orbital mass and renal failure is described. Myeloma patients can present to any physician with any specialty. Renal impairment is quite common in myeloma. Early recognition of this complication is important in preserving the kidneys. The patient was treated with Bortezomib and Dexamethasone and had good initial response to treatment.

Multiple Myeloma

2014 ◽  
pp. 151-164
Author(s):  
Constantine S. Mitsiades ◽  
Kenneth C. Anderson ◽  
Paul G. Richardson
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Lymphoproliferative Disease ◽  
M Protein ◽  
Plasma Cell Dyscrasia ◽  
Transformation Rate ◽  
Clonal Population ◽  
Premalignant Condition ◽  
Undetermined Significance

Multiple myeloma (MM) is a clonal accumulation of malignant plasma cells (PCs) that typically produce a monoclonal immunoglobulin (Ig) (or fragment thereof), termed M-protein, detectable in the serum or urine. Despite recent advances in its treatment (median overall survival is now 5–7 years, compared to 2–3 years for patients diagnosed 10 or more years ago), MM remains incurable. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition in which a clonal population of plasma cells accumulates in the bone marrow (BM). MGUS is asymptomatic and does not otherwise meet diagnostic criteria for MM, but it can develop into MM, other plasma cell dyscrasia, or lymphoproliferative disease with a transformation rate of approximately 2% per year.

scholarly journals Comparison of Monoclonal Gammopathies Linked to Poliovirus or Coxsackievirus vs. Other Infectious Pathogens

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 438
Author(s):  
Jean Harb ◽  
Nicolas Mennesson ◽  
Cassandra Lepetit ◽  
Maeva Fourny ◽  
Margaux Louvois ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Monoclonal Gammopathy ◽  
Coat Proteins ◽  
Chronic Stimulation ◽  
B Cell Epitopes ◽  
Monoclonal Immunoglobulins ◽  
Self Antigen ◽  
Coxsackievirus B1 ◽  
Undetermined Significance

Chronic stimulation by infectious pathogens or self-antigen glucosylsphingosine (GlcSph) can lead to monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Novel assays such as the multiplex infectious antigen microarray (MIAA) and GlcSph assays, permit identification of targets for >60% purified monoclonal immunoglobulins (Igs). Searching for additional targets, we selected 28 purified monoclonal Igs whose antigen was not represented on the MIAA and GlcSph assays; their specificity of recognition was then analyzed using microarrays consisting of 3760 B-cell epitopes from 196 pathogens. The peptide sequences PALTAVETG and PALTAAETG of the VP1 coat proteins of human poliovirus 1/3 and coxsackievirus B1/B3, respectively, were specifically recognized by 6/28 monoclonal Igs. Re-analysis of patient cohorts showed that purified monoclonal Igs from 10/155 MGUS/SM (6.5%) and 3/147 MM (2.0%) bound to the PALTAVETG or PALTAAETG epitopes. Altogether, PALTAV/AETG-initiated MGUS are not rare and few seem to evolve toward myeloma.

Towards personalised management for non-variceal upper gastrointestinal bleeding

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323846
Author(s):  
Joseph J Y Sung ◽  
Loren Laine ◽  
Ernst J Kuipers ◽  
Alan N Barkun
Keyword(s):  
Gastrointestinal Bleeding ◽  
Upper Gastrointestinal Bleeding ◽  
Point Of Care ◽  
Management Strategies ◽  
Patient Characteristics ◽  
Professional Societies ◽  
Assessment And Treatment ◽  
Three Stages ◽  
Endoscopic Assessment ◽  
Upper Gastrointestinal

Guidelines from national and international professional societies on upper gastrointestinal bleeding highlight the important clinical issues but do not always identify specific management strategies pertaining to individual patients. Optimal treatment should consider the personal needs of an individual patient and the pertinent resources and experience available at the point of care. This article integrates international guidelines and consensus into three stages of management: pre-endoscopic assessment and treatment, endoscopic evaluation and haemostasis and postendoscopic management. We emphasise the need for personalised management strategies based on patient characteristics, nature of bleeding lesions and the clinical setting including available resources.

scholarly journals Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Controlled Trial ◽  
Participation Rate ◽  
Population Based ◽  
Early Therapy ◽  
Screening Study ◽  
Undetermined Significance

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

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