Clinical Presentation Of Multiple Myeloma Research Articles

Prediction of Malignant Cell Infiltration Patterns with Texture Features of Biopsy-Correlated Positron Emission Tomography of Osteolytic Lesions in Multiple Myeloma

Prediction of Malignant Cell Infiltration Patterns with Texture Features of Biopsy-Correlated Positron Emission Tomography of Osteolytic Lesions in Multiple Myeloma

Clinical presentation of multiple myeloma by race/ethnicity and Asian subgroup in an integrated healthcare system.

e20012 Background: Several US studies have evaluated ethnic differences in patients with multiple myeloma (MM), but few have focused on populations other than non-Hispanic Whites and Blacks. We examined ethnic differences in a contemporary cohort of MM patients and their presenting laboratory findings in a large, insured, community-based population, including findings across Asian American subgroups. Methods: Using the Kaiser Permanente Northern California (KPNC) Cancer Registry, we identified all new cases of MM from 2010-2018 and obtained data on age, sex, race/ethnicity, Asian subgroup, and presenting hemoglobin, calcium, and estimated renal function (eGFR derived from serum creatinine) from health plan databases. Moderate to severe anemia was defined by hemoglobin <10 g/dL, hypercalcemia by calcium >11 mg/dL, and chronic kidney disease (CKD) by eGFR: stage 3 (eGFR 30-59) and stages 4-5 (eGFR <30). MM incidence was estimated using membership denominators. Results: There were 2224 new MM cases (mean age 68y, 60% male) in 2010-2018, with an annual MM incidence of 7.9-9.8/100,000. Table 1 compares presentation by race/ethnicity. Non-Whites (45%) were more likely to present at age <65 than non-Hispanic Whites (30%, p<0.01). Black (43%) and Asian (39%) adults were more likely to present with hemoglobin <10 g/dL than non-Hispanic Whites (27%, p<0.01); Black adults were more likely to present with hemoglobin <10 g/dL than Hispanic adults (31%, p=0.02). Among the primary Asian subgroups, proportions with hemoglobin <10 g/dL were 38% (East Asian), 43% (Filipino), and 45% (South Asian). Blacks were more likely to present with CKD stage 4-5 (19.5%) than other races/ethnicities (p=0.04); differences between White vs non-White or Asian vs non-Asian were not significant. In Asians, 12.7% (South Asian) and 19.0% (Filipino, East Asian) presented with CKD 4-5. Asians were least likely to present with hypercalcemia (6.7%, p=0.03), and this was similar for Asian subgroups. Conclusions: We observed ethnic differences in MM presentation in a large integrated healthcare system. Blacks were more likely to have CKD stage 4-5 and hemoglobin <10 g/dL than non-Hispanic Whites. Asians were more likely to have CKD stage 4-5 than non-Hispanic Whites but least likely to have hypercalcemia. This is one of the first studies to identify Asian subgroups and examine variation across East Asians, Filipinos, and South Asians. Analyses examining ethnic differences in survival among MM patients are in progress.[Table: see text]

Association between Clinical Presentation of Multiple Myeloma, Immunoglobulin Isotypes, and Cytogenetic Risk Groups

Introduction: In multiple myeloma (MM), chromosomal abnormalities (CAs) are valuable in risk stratifying patients and predicting disease free survival. While immunoglobulin isotypes have historically contributed to MM staging, more recently established classifications of CAs have allowed for a revised staging system that better predicts disease behavior. In this retrospective study, we hypothesized that CAs correlate with disease characteristics including immunoglobulin heavy chain isotype, degree of bone marrow infiltration (PC%), and end-organ damage. Methods: MM patients diagnosed between 2013 to 2019 were included in this retrospective chart review using electronic records from two distinct sources: (1) 442 patients from an independent pathology database and (2) a validation cohort composed of 110 patients from our institution. CAs were stratified by Mayo mSMART 2.0 criteria into standard, intermediate, and high-risk groups (Mikhael et al. Mayo Clin Proc 2013). End-organ damage was defined as the presence of lytic bone lesions, anemia, hypercalcemia, or renal failure on clinical presentation. Within each cohort, associations between categorical variables were made using the chi-squared test or Fisher's exact test, as deemed appropriate. The Mann-Whitney test was used to compare between groups for continuous variables. A result was considered statistically significant at the p<0.05 level of significance. All analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC). Results: 552 MM patients were included in the study. Multi-variate analysis revealed that del(13q14), dup(1q21), t(4;14), trisomy (11q13), del(16q23), and hypodiploidy were associated with a significantly higher PC%, whereas kappa light chain only (LCO) disease was associated with a lower PC%. Higher median PC% was found when comparing the intermediate to standard CA risk group. IgA isotype was associated with intermediate risk CAs including del(13q) and standard risk CAs including t(11;14), while IgG isotype was associated with dup(1q21), and kappa LCO disease correlated with a higher rate of higher risk CAs including deletion of p53 at 17p13 and dup(1q21). With regard to clinical presentation, lytic lesions were more frequent in patients with normal cytogenetics and trisomy 11 and less frequent in IgA isotype, whereas the presence of anemia on presentation correlated with IgA isotype. Renal failure was associated with MAF translocations including t(14;16), a high-risk CA. Conclusions: We demonstrate that a relationship exists between specific CAs, immunoglobulin isotypes, and clinical presentations in MM. Our data indicate that IgA isotype is significantly associated with intermediate-risk cytogenetics including del(13q) and anemia on presentation, and that light chain disease and renal failure correlate with high risk CAs including del(17p13). These associations between biological and clinical features further support the concept of divergent cytogenetic evolution in MM as being an underlying factor leading to distinctive disease presentations. Disclosures Braunstein: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

An approach to the diagnosis and management of multiple myeloma

Multiple myeloma (MM) is a plasma cell dyscrasia that accounts for ~10% of haematological malignancies. It is a disease of the elderly, with a slight male predominance. Almost all cases of MM are preceded by an asymptomatic, premalignant phase known as monoclonal gammopathy of undetermined significance (MGUS). The clinical presentation of MM may be nonspecific, with the most common presenting symptoms being fatigue, bone pain and anaemia. The diagnostic criteria for MM were revised in 2014 to include 3 specific biomarkers of malignancy that are associated with an increased risk of target organ damage. This has resulted in a paradigm shift in the management of MM. The introduction of immunomodulatory agents and proteasome inhibitors has significantly improved the survival of patients with MM. Autologous stem cell transplantation remains the standard of care in younger, fit patients, where there is also a clear role for maintenance chemotherapy. Transplant-ineligible patients benefit from a prolonged induction therapy, and the role of maintenance therapy in this setting is still unclear. Despite major advances in therapy, MM remains an incurable malignant condition and novel agents such as monoclonal antibodies play an important role, especially in the elderly and patients who have relapsed.

Objawy choroby tkanki łącznej u chorej ze szpiczakiem plazmocytowym – opis przypadku

Wstęp: Szpiczak plazmocytowy jest chorobą nowotworową układu limfatycznego, która charakteryzuje się proliferacją i gromadzeniem monoklonalnych plazmocytów wytwarzających zwykle monoklonalną immunoglobulinę. Występuje najczęściej u ludzi starszych. Pierwsze objawy są nieswoiste, należą do nich m.in. bóle kostne oraz osłabienie związane z niedokrwistością. W zaawansowanym klinicznie szpiczaku objawy wynikają na ogół ze współwystępowania zmian osteolitycznych, a także złamań patologicznych. Szpiczak może przypominać obraz wielu innych chorób, w tym także chorób reumatycznych.Opis przypadku: Przedstawiono przypadek chorej, która zgłaszała objawy choroby tkanki łącznej w przebiegu szpiczaka plazmocytowego.Wnioski: Objawy układowej choroby tkanki łącznej mogą wyprzedzać lub maskować objawy choroby nowotworowej. W przypadkach niecharakterystycznego przebiegu zawsze należy poszerzyć diagnostykę w kierunku procesu rozrostowego.

The Association of International Staging System (ISS) Stage with Disease and Symptom Burden in Patients with Newly Diagnosed Multiple Myeloma

Background: The clinical presentation of multiple myeloma (MM) varies greatly but often includes bone pain, anemia, renal dysfunction, hypercalcaemia, and/or constitutional symptoms. There are no signs or symptoms that are disease specific. The earliest staging system for MM, the Durie-Salmon (DS), associated disease and symptom burden with prognosis; however, it has been largely replaced by the International Staging System (ISS), which is easier to compute and better identifies patients with the poorest prognosis. It is unclear if ISS stage, like DS, is associated with disease or symptom burden.Objective: To compare disease and symptom burden of patients with newly diagnosed MM by ISS Stage.Methods: Data was extracted from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway corresponding with interim analysis 6 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data and patient reported quality of life (EORTC QLQ-C30 and QLQ-MY20), as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator and/or a proteasome inhibitor for initial MM treatment; and no prior malignancies in the past 5 years.All clinical data was reported by trained data analysts at the enrolling center with the exception of flow cytometry which was performed centrally; raw lab values for beta-2 microglobulin and albumin were entered and stage was subsequently calculated by the analysts for this study according to the ISS (Greipp et al, JCO 2005). Twenty-six patients with unknown ISS were excluded from the analysis. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with one-way ANOVA tests.Results: 599 patients were eligible for analysis. Sex, race, and heavy and light chain isotypes were all evenly distributed among the ISS stages; however, median age for ISS stage III was 67, 65 for stage II and 62 for stage I (p<0.001). Stage I and II patients were similar in disease burden, but stage III patients had higher serum M-proteins (p<0.001), LDH (p=0.002), bone marrow plasma cells (p<0.001), circulating plasma cells (p<0.001), and creatinine (p<0.001), and lower hemoglobin (p<0.001) and platelets (p=0.001). Further, stage III patients had poorer performance status (p<0.001), global health (p<0.001), physical functioning (p<0.001), social functioning (p<0.001), and role functioning (p<0.001), and increased fatigue (p<0.001) and pain (p=0.016). Results are summarized in Table 1.Conclusions: Stage III had a higher disease and symptom burden than stage I and II patients. Stage I and II patients were similar in most measures suggesting that ISS may not discriminate between these groups well, this is supported by other studies that have failed to find outcomes differences between stage I and II patients.Table 1Stage I n= 204Stage II n = 210Stage IIIn = 185pDemographicsAge in years626567<0.001Male64%57%62%NSRaceNSWhite80%83%74%Black19%13%23%Other2%3%3%Heavy ChainNSIgG80%80%75%IgA20%20%25%Light ChainNSKappa65%61%60%Lambda34%38%38%Biclonal1%2%2%Disease BurdenSerum M-Protein g/dL1.92.03.2<0.001LDH μkat/L2.72.83.00.002Bone Marrow Plasma Cells*7%9%13%<0.001Circulating Plasma Cells*0%0%0.1%<0.001Calcium mmol/L2.42.32.4<0.001Creatinine μmol/L8288149<0.001Hgb mmol/L7.46.45.8<0.001Platelets x109/L222212199.001Bone Lesions61%52%53%NSSymptom Burden/Quality of Life MeasuresECOG Performance Status<0.001047%42%22%149%42%54%25%8%15%3-40%8%9%Global Health Scale666650<0.001Physical Functioning Scale868063<0.001Cognitive Functioning Scale838383NSEmotional Functioning Scale757575NSSocial Functioning Scale838366<0.001Role Functioning Scale666650<0.001Disease Symptom Scale272227NSFatigue Scale333344<0.001Pain Scale3333420.016Note-Median presented unless specified.*- CD38+/CD138+ by flow cytometry DisclosuresVij:Takeda, Onyx: Research Funding; Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy.

Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma

An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

Amyloidosis of the Tongue: As the First Clinical Presentation of Multiple Myeloma

Amyloidosis of the Tongue: As the First Clinical Presentation of Multiple Myeloma

Clinical, Immunophenotypic, and Genetic Characterization of Small Lymphocyte–Like Plasma Cell Myeloma

We reviewed bone marrow studies from 351 multiple myeloma (MM) cases, selecting 12 cases (3.4%) with predominantly small lymphocyte-like morphologic features resembling B-cell lymphoma, and correlated their genetic and clinical features. All exhibited a diffuse interstitial pattern of marrow involvement. Small lymphocyte-like plasma cells were all CD45- with bright CD38 and CD138 expression and CD20 expression in 5 cases. No case had an increase in bone marrow B lymphocytes by flow cytometry. Of 12 cases, 9 were classified as the CD-2 molecular class by gene expression profiling (GEP). The 29 CD-2 class cases with (n = 9) and without (n = 20) small lymphocyte-like features could not be discerned from one another using global GEP. Event-free, but not overall, survival was significantly better in cases with small lymphocyte-like features among those sharing the CD-2 subtype. Small lymphocyte-like MM is a rare, morphologically challenging variant distinguished from B-cell lymphoma by lack of CD45 and presence of CD138 and the clinical presentation of MM. Most cases share a common GEP signature dominated by hyperexpression of cyclin D1 or cyclin D3 genes, with increased expression of the B-cell genes CD20 and VPREB3.

Changes in multiple myeloma epidemiology in the last thirty years: A single centre experience

In this study we have evaluated 772 multiple myeloma (MM) patients for clinical presentation, response to treatment, relapse modality, and survival in the last 30 years. Patients were divided, according to the date of diagnosis in group I or group II (before and after 1994, respectively) and therapy (high or conventional dose). Bone pain and early deaths were statistically reduced in group II, whereas MM that evolved from monoclonal gammopathy of undetermined significance (MGUS) had increased. The efficacy of high dose therapy (HDT) over conventional dose therapy (CDT) was confirmed through analysis of response rate, progression free, and overall survival. Relapse modality was similar after HDT or CDT. Among older patients, those diagnosed after 1994 lived longer than those diagnosed before 1994. In the last 30 years, the clinical presentation of multiple myeloma remained substantially unchanged. The new therapeutic approaches, chemotherapy and supportive therapy, allowed better control of the disease with an improvement of survival.

Changing clinical presentation of multiple myeloma

We compared the presentation features of three series of patients with multiple myeloma diagnosed between 1960 and 1971 (Kyle R, Mayo Clin Proc, 1975, 50, 29, n = 869), 1972 and 1986 (Clinica Medica, University of Pavia, n = 345) and 1987 and 1990 (Cooperative Group for Study and Treatment of Multiple Myeloma, n = 341). In the most recently diagnosed patients, the percentage of those who had symptoms related to multiple myeloma (i.e. any of bone pain, systemic symptoms, disturbances related to hypercalcemia, neurological involvement and hyperviscosity) was reduced (90 vs. 86 vs. 66%) ( P < 0.001), while the percentage of asymptomatic patients diagnosed by chance was increased (not reported, and 14 vs. 34%). In the most recent series, a lower percentage of spontaneous bone pain (68 vs. 60 vs. 37%, P < 0.001) paralleled a lower incidence of advanced bone disease (osteolyses and pathological fractures, 60 vs. 64 vs. 34%), and renal failure (serum creatinine > 1.2 mg/dl) was also less common (56 vs. 44 vs. 33%, P < 0.01), at least partially due to a decreased incidence of both hypercalcemia (30 vs. 20 vs. 18%, P < 0.001) and of hyperuricemia (serum uric acid >7 mg/dl, 47 vs. 32 vs. 26%, P < 0.01). Systemic symptoms (weakness, infections, fever or weight loss) were reported more seldom by recently diagnosed patients, due to a decreased frequency of anaemia (haemoglobin < 12 g/dl), leukopenia and thrombocytopenia, as well as of the systemic effects of bone pain and of renal insufficiency. These data indicate that multiple myeloma is diagnosed earlier now than in the past, and this must be taken into account when comparing survival data in treated series.