Characteristics Of Multiple Myeloma Patients Research Articles

The numerous facets of 1q21+ in multiple myeloma: Pathogenesis, clinicopathological features, prognosis and clinical progress (Review).

Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal proliferation of abnormal plasma cells (PCs) in the bone marrow and recurrent cytogenetic abnormalities. The incidence of MM worldwide is on the rise. 1q21+ has been found in ~30-40% of newly diagnosed MM (NDMM) patients.1q21+ is associated with the pathophysiological mechanisms of disease progression and drug resistance in MM. In the present review, the pathogenesis and clinicopathological features of MM patients with 1q21+ were studied, the key data of 1q21+ on the prognosis of MM patients were summarized, and the clinical treatment significance of MM patients with 1q21+ was clarified, in order to provide reference for clinicians to develop treatment strategies targeting 1q21+.

Characteristics of Multiple Myeloma Patients on Dialysis Who Receive Autologous Stem Cell Transplant

Characteristics of Multiple Myeloma Patients on Dialysis Who Receive Autologous Stem Cell Transplant

Risk Factors and the Effect of Antiviral Prophylaxis for Herpes Zoster in Multiple Myeloma Patients

To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy. The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed, the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed. Among 180 patients with multiple myeloma, 23 cases developed herpes zoster (12.8%). The incidence of herpes zoster was 19.1% in patients with renal dysfunction and 23.5% after autologous hematopoietic stem cell transplantation (ASCT). The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens (21/137, 15.3%) than that in those without bortezomib (2/43, 4.7%), but there was no statistical difference (P =0.067). Antiviral prophylaxis was associated with fewer zoster infections, 8/111(7.2%) developed herpes zoster in patients who received antiviral prophylaxis, and 15/69 (21.7%) in those receiving no prophylaxis(P =0.005). 65.2% of patients with herpes zoster did not receive antiviral prophylaxis. Multivariate analysis showed that bortezomib treatment, AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster, while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster. Herpes zoster had no effect on OS in patients with multiple myeloma. The risk of herpes zoster in multiple myeloma patients was increased. Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.

Descriptive Characteristics of Multiple Myeloma Patients in King Abdulaziz Medical City National Guard.

Background Multiple myeloma (MM) is a hematological malignancy characterized by the production of monoclonal immunoglobulin. It is the second-most common hematological malignancy. The survival rate varies depending on age at diagnosis, comorbidities, and treatment.This study aims to assess the prevalence of clinical and laboratory characteristics among multiple myeloma patients. Methods This is an observational study of multiple myeloma patients who were admitted to King Abdulaziz Medical City - National Guard between January 2015 and December 2020. Patient records were reviewed to derive clinical and laboratory characteristics. Descriptive data analysis and survival analysis were obtained using SPSS. Results Our study included 151 patients, 95 of whom were males and 56 were females, and the mean age of diagnosis with MM was 62.6 (SD = 13.4). Among 151 MM patients, the most common clinical signs were bone lesions and renal disease, with a percentage of 66.9% and 46.4%, respectively. Death rates throughout the time of study conduction were 19.2%, accounting for 29 patients, and the median overall survival was 5.1 years with a 95% confidence level. Testing the association between survival rates and gender showed that death rates in females were significantly higher than in males (p-value = 0.023). Patients with anemia had a significantly higher hazard ratio in both unadjusted and adjusted analyses (aHR = 2.61; 95% CI = 1.21-5.65). Conclusion There was a relationship between survival and gender, which suggests a protective factor favoring the male gender. Clinical and laboratory characteristics, including bone marrow lesions, anemia, and renal disease, were the initial presentation; thus, a detailed history focused on symptoms should be taken when any of these symptoms are reported.

Clinical profiles in multiple myeloma patients with extreme survivals: a study from a National Medical Center in China

ABSTRACT Objectives The clinical outcomes of multiple myeloma (MM) patients are highly variable in the real-world setting. Some MM patients may have clinical endings that do not abide by the book. We aim to describe features of MM patients with extreme survivals in real-world practice. Methods This retrospective study enrolled 941 patients consecutively visited a national medical center, China, between July 1995 and December 2021. Among patients, we identified two groups of MM patients with extreme survivals, 56 were in the long-term remission (LR) group with progression-free survival (PFS) ≥ 60 months, and 82 were in the rapid progression (RP) group with PFS ≤ 6 months. Results CRAB features, of which hypercalcemia, renal insufficiency, and anemia were more common in the RP group, except for bone disease, with a comparable incidence at diagnosis in both groups (88.8 vs 85.7%, P = 0.52). High-risk cytogenetics was detected in 45.7% of patients in the RP group. Of note, 14.3% of MM patients in the LR group harbored del (17p). According to the Revised International Staging System (R-ISS), 9% of patients belonged to stage I in the RP group, and 19% of patients in the LR group were found in stage III. There were 8 (15.7%) patients in the LR group only achieved partial response (PR) as the best response. Median time to best response (TBR) for LR and RP group patients was 4.6 and 1.4 months, respectively. Conclusions The disparities in the survivals of MM patients indicated that some unexpected factors have influenced the outcomes in the real-world setting.

MiR-26 inhibits proliferation and promotes apoptosis of multiple myeloma cells by targeting BNIP3.

This study was carried out to investigate the molecular mechanism of microRNA-26 (miR-26) targeting BNIP3 to mediate proliferation and apoptosis of multiple myeloma (MM) cells. The expression of miR-26 and BNIP3 in MM and normal tissues was detected by qRT-PCR and Western blot. According to the average expression of miR-26 and BNIP3, the patients were divided into 12 cases with high miR-26 expression group, 18 cases with low miR-26 expression group, 20 cases with BNIP3 high expression group, and 10 cases with BNIP3 low expression group. The correlation between the expression of miR-26 and BNIP3 and the clinicopathological characteristics of MM patients was compared and analyzed. The effect of up-regulation of miR-26 expression and BNIP3 overexpression on the proliferation of multiple myeloma cells RPMI8226 was examined by MTT assay. Flow cytometry was used to detect the effect of miR-26 expression and BNIP3 overexpression on the apoptosis of RPMI8226 cells. The dual luciferase reporter assay validated the targeted regulation of miR-26 on BNIP3. The expression level of miR-26 in MM tissues was lower than that in normal tissues (P<0.05), and the expression level of BNIP3 in MM tissues was higher than that in normal tissues (P<0.05). miR-26 was closely related to clinical stage, M protein type and light chain type (P<0.05), while BNIP3 was closely related to M protein type and light chain type (P<0.05). After up-regulating miR-26 expression, cell viability was significantly decreased (P<0.05), apoptosis rate was significantly increased (P<0.05) Dual luciferase reporter experiments confirmed that miR-26 could target BNIP3 and negatively regulate the expression of BNIP3 (P<0.05). Overexpression of BNIP3 reversed the effect of up-regulation of miR-26 expression on proliferation and apoptosis of RPMI8226 cells. Up-regulation of miR-26 expression inhibits MM cell proliferation and promotes apoptosis by targeting BNIP3.

Primary or Secondary Plasma Cell Leukemia: Dismal Outcome Despite Modern Treatments

BACKGROUND Plasma cell leukemia (PCL) is a rare and aggressive plasma cell dyscrasia, associated with short survival. This disease is usually divided into primary PCL (pPCL), when occurring de novo, or secondary PCL (sPCL), when a patient previously diagnosed with multiple myeloma (MM) undergoes leukemic transformation. Because of the very low incidence of PCL, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand PCL, particularly in regard to the characteristics of MM before leukemic transformation and the outcomes following modern treatments in both pPCL and sPCL. METHODS We performed a retrospective, multicenter study of patients diagnosed with PCL between January 2005 and December 2020 in eight institutions in the Province of Québec, Canada. Patients were identified through digital medical records. The 2013 International Myeloma Working Group (IMWG) diagnostic criteria for PCL (circulating plasma cells ≥ 20% and/or ≥ 2 x 10 9/L) were used to determine eligibility. Patients were excluded if they received treatment for another malignancy after the diagnosis of PCL. RESULTS We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. Among significant clinical characteristics, both pPCL and sPCL patients showed a high frequency of thrombocytopenia, splenomegaly, and light chain isotype (Table I). At MM diagnosis, patients who eventually progressed to sPCL were much younger (median 61.8 years) than a typical MM cohort and many of them already demonstrated markers of poor prognosis, including elevated lactate dehydrogenase (LDH), elevated ß 2-microglobulin and complex cytogenetics (Table I). The median time between initial MM diagnosis and leukemic progression was 27.3 months (IQR, 12.7 - 41.6). The median number of lines of treatment prior to transformation was 2 (range 1 - 7). Overall, autologous stem cell transplant (ASCT; n = 28) or tandem ASCT-allogeneic stem cell transplant (ASCT-alloSCT; n = 4) did not result in longer time to PCL progression when compared to those who received chemotherapy alone (31.6 vs 22.9 months, p = 0.164). Median overall survival (OS) for pPCL and sPCL were respectively 18.3 months (95% CI, 0.0 - 39.0) and 1.2 months (95% CI, 0.9 - 1.5) (p &amp;lt; 0.001). When considering survival from MM diagnosis to death, the median OS for sPCL was 30.2 months (95% CI, 24.1 - 36.2). Patients with pPCL who underwent ASCT or tandem ASCT-alloSCT had a significantly longer OS than patients treated with chemotherapy alone (HR 0.27, 95% CI 0.11 - 0.64, p = 0.003). The impact of stem cell transplant on sPCL survival could not be assessed, as only one of 66 sPCL patients received this type of treatment. The median number of lines of treatment was 2 (range 1 - 9) for pPCL and 1 (range 0 - 5) for sPCL. Interestingly, patients receiving more recent regimens (2013-2020) did not have a better OS than patients receiving earlier treatments (2005-2012) (p = 0.391). When analysed separately, OS for pPCL or sPCL did not improve significantly in the later period (Figure 1). Clinical characteristics independently associated with poor outcomes were sPCL subtype and elevated LDH (respectively, HR 4.9, 95% CI 2.2 - 11.9, p &amp;lt; 0.001 and HR 2.4, 95% CI 1.0 - 5.7, p = 0.049). Although expression of CD19 and/or CD20 was not statistically significant in multivariable analysis, a trend towards improved survival was observed in patients expressing these markers (HR 0.4, 95% CI 0.1 - 1.1, p = 0.062). CONCLUSION This retrospective, multicenter study is one of the largest PCL cohorts reported and we are, to our knowledge, the first to investigate characteristics of MM patients before their transformation into sPCL. Although this subgroup is often described as a late-stage complication of heavily pretreated MM, our data suggest that sPCL originates from an already high-risk MM population rather than being the result of long-term selection of an aggressive clone. More information is however needed for early identification of MM patients at risk of PCL transformation. Finally, despite the use of newer chemotherapy regimens, we observed no improvement in OS in recent years, highlighting the urgent need for better treatment options for both pPCL and sPCL.

P-151 Demographic and clinical characteristics of multiple myeloma patients in a tertiary cancer institute of India

P-151 Demographic and clinical characteristics of multiple myeloma patients in a tertiary cancer institute of India

NSO-02 Characteristics of multiple myeloma patients with central nervous system involvement

NSO-02 Characteristics of multiple myeloma patients with central nervous system involvement

257 - The Characteristics of Multiple Myeloma Patients Referred for CAR T-Cell Therapy

257 - The Characteristics of Multiple Myeloma Patients Referred for CAR T-Cell Therapy

Demographic and Clinical Characteristics of Multiple Myeloma Patients in Latin America

Background: Multiple myeloma (MM) is characterized by uncontrolled proliferation of plasma cells. This condition accounts for 1% of all cancers and 13% of all hematologic malignancies (HMs). In Latin America there is a relative paucity of real-world data of MM patients. Therefore, the objective of this study is to describe the demographic and clinical characteristics of multiple myeloma patients in Latin America. Methods: This is an ongoing, noninterventional, multicenter, registry study. Patients diagnosed with MM between 01 January 2016 and 30 June 2021, age ≥ 18 years were enrolled and will be followed until death or the end of study (set for 30 June 2022). For this interim analysis the demographic and clinical data of MM patients in a real-world setting in five Latin American countries, Argentina, Brazil, Mexico, Colombia, and Panama, were assessed. The retrospective data are being abstracted from patient's medical records. All statistical analyses were descriptive. Results: From a total of 1076 enrolled patients, 984 were assessed (Argentina= 287; Brazil= 428; Colombia= 253; Mexico= 13; Panama= 3). 64.9% of the patients have private insurance coverage, and 35.1% belongs to the public treatment system. The median age at diagnosis was 63 years and a similar distribution between male (49.3%) and female (50.7%) was observed. The majority of the patients (78.7%) presented at least one comorbidity, with hypertension (62.2%) and diabetes (21.1%) the most common medical conditions observed. Around 32% of the patients were considered clinically non-eligible to autologous stem-cell transplantation (ASCT, intention to treat), and advanced age was the main reported reason (median 76 years for non-eligible). Back pain and bone pain were the most frequently reported symptoms at diagnosis by 44.5% and 30.5% of the patients, respectively. Consequently, many patients were referred by orthopedists (20.6%). At diagnosis, the distribution of ECOG status was 0= 38.8%, 1= 32%, 2= 17.6%, 3= 8% and 4= 3.6%; and the ISS 1= 27.4%, 2= 28.6% and 3= 44%. Among the population with a cytogenetic test performed (n=462), only 27.7% were positive for any alteration. The most frequent alterations observed were t(4;14) translocation and del(17p), affecting 39 and 42 patients, respectively. In Table 1 are the clinical and demographic characteristics according to country of enrollment. Conclusion: These results are a portrait of multiple myeloma in Latin America, showing that patient's characteristics are quite similar among the participating countries. Although the majority of the MM patients in Latin America receive the treatment in the public institutions, in this cohort there were more patients came from private institutions. The most common symptom reported at diagnosis was associated with bone disease and the majority of the patients presented advanced disease (ISS 3 = 44%). Only 32% was considered non-eligible for ASCT at diagnosis. It is worth noting that most of the patients did not present any genetic alterations, which may impact in the identification of higher risk disease. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical and Demographic Characteristics of Multiple Myeloma Patients at Study Enrollment: Analysis of Doriant Study (NCT:04659798)

BACKGROUND: Multiple Myeloma is a heterogenous disease characterized by subsequent relapses in which the burden of the disease and previous treatments received could limit subsequent lines of therapy, as described in treatment guidelines. The disease becomes more aggressive after each relapse and the time between relapses is shorter, which means less duration of response per late line of treatment that could lead into treatment refractoriness. Progression free survival is shorter after each treatment line and the prognosis of the patients gets worse. Increasing the DoT at relapse has a positive impact in the overall survival (OS) and in the clinical evolution of the disease. However, duration of treatment (DoT) is not reported outside clinical trials and there is a lack of information in clinical practice. There is increasing evidence to Support a treatment paradigm shift from the traditional fixed duration strategy to a continuous therapy approach to improve outcomes. The determinants of DoT and its relationship with survival in real-life practice have been little investigated, including reasons for treatment discontinuation. This research aims to investigate the relationship between DoT and outcomes in clinical practice, also analyzing the satisfaction with the treatment received from patients with MM and AL amyloidosis as an exploratory endpoint. OBJECTIVE: To investigate the relationship between DoT and response according to selected treatment strategy (fixed vs continuous) among patients diagnosed with MM and/or AL amyloidosis. We provide an update regarding baseline characteristics of the MM population enrolled in the study as per the information collected during the entry study visit. METHODS: Prospective, non-interventional, multi-centre study in real-life practice in 14 Spanish hospitals. The study enrolled subjects aged 18 or older diagnosed with MM and/or AL amyloidosis who started treatment up to 12 months before the inclusion. The study has enrolled a total of 240 patients, 207 of them with MM diagnosis. RESULTS: Of the 207 MM enrolled patients, 191 (92,3%) were eligible for this analysis. 106 (55.5%) were at 1L of treatment, 52 (27.2%) at 2L, 24 (12.6%) at 3L and 9 (4.7%) at subsequent lines. 30 patients were at maintenance setting. The median age was 74 (67,79) years, 93 (48,7%) were male and 98(51,3%) were female. 142 (75,1%) lived in urban areas, 16 (8.9%) patients lived alone, 154 (86%) with the family and 9 (5%) requires support from a caregiver. At study entry, 143 (78.1%) were independent, 25 (13.7%) grade I, 12 (6.6%) grade 2 and 3(1.6%) grade 3. 42 patients (22.3%) have primary studies, 14 (7.5%) were in active employment, 11 (5.9%) unemployed and 146 (78.5%) were retired. Physical activity was high in 10 (5.5%) patients, 102 (56.4%) moderate/low and 69 (38.1%) were inactive. Comorbidities are listed in Table 1. 44.5% of the patients have received a previous line of treatment and 60 (31.6%) has received a previous stem cell transplant (SCT) at study visit. Laboratory and cytogenetic test were available in 189 patients at study entry. 25 (13.3%) have minimal residual disease (MRD) test available with 9.6% positive and 3.7% negative. 90 (47.6%) patients performed a cytogenetic abnormalities test at current treatment initiation, 39 (43.3%) with high risk and 51 (56.7%) with standard risk. ECOG at current treatment initiation was available in 89 patients, 23 (25.8%) ECOG 0, 56 (62.9%) ECOG 1 and 7 (7.9%) ECOG 2. In 190 patients Charlson Comorbidity Index was performed at current treatment initiation and 184 patients completed the TSQM questionnaire. Prescribed regimens per line and main agent are listed in table 2. 41 (21,5%) patients received a fixed duration vs 150 (78,5%) continuous treatment strategy. CONCLUSION: Based on this preliminary analysis in the MM eligible population, the majority of patients are under a continuous treatment strategy, are in early treatment lines and the current treatment received is based on monoclonal antibodies as main agent. Further analysis will be provided to determine treatment patterns per line and duration of treatment prescribed in real-life practice. Keywords: multiple myeloma (MM); clinical characteristics, duration of treatment, fixed and continuous treatment, real-life practice. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF MULTIPLE MYELOMA PATIENTS IN LATIN AMERICA

Multiple myeloma (MM) is characterized by uncontrolled proliferation of plasma cells. This condition accounts for 1% of all cancers and 13% of all hematologic malignancies (HMs). In Latin America there is a relative paucity of real-world data of MM patients. Therefore, the objective of this study is to describe the demographic and clinical characteristics of multiple myeloma patients in Latin America. This is an ongoing, noninterventional, multicenter, registry study. Patients diagnosed with MM between 01 January 2016 and 30 June 2021, age ≥ 18 years were enrolled and will be followed until death or the end of study (set for 30 June 2022). For this interim analysis the demographic and clinical data of MM patients in a real-world setting in five Latin American countries, Argentina, Brazil, Mexico, Colombia, and Panama, were assessed. The retrospective data are being abstracted from patient's medical records. All statistical analyses were descriptive. From a total of 1076 enrolled patients, 984 were assessed (Argentina= 287; Brazil= 428; Colombia= 253; Mexico= 13; Panama= 3). 64.9% of the patients have private insurance coverage, and 35.1% belongs to the public treatment system. The median age at diagnosis was 63 years and a similar distribution between male (49.3%) and female (50.7%) was observed. The majority of the patients (78.7%) presented at least one comorbidity, with hypertension (62.2%) and diabetes (21.1%) the most common medical conditions observed. Around 32% of the patients were considered clinically non-eligible to autologous stem-cell transplantation (ASCT, intention to treat), and advanced age was the main reported reason (median 76 years for non-eligible). Back pain and bone pain were the most frequently reported symptoms at diagnosis by 44.5% and 30.5% of the patients, respectively. Consequently, many patients were referred by orthopedists (20.6%). At diagnosis, the distribution of ECOG status was 0= 38.8%, 1= 32%, 2= 17.6%, 3= 8% and 4= 3.6%; and the ISS 1= 27.4%, 2= 28.6% and 3= 44%. Among the population with a cytogenetic test performed (n = 462), only 27.7% were positive for any alteration. The most frequent alterations observed were t(4;14) translocation and del(17p), affecting 39 and 42 patients, respectively. These results are a portrait of multiple myeloma in Latin America, showing that patient's characteristics are quite similar among the participating countries. Although the majority of the MM patients in Latin America receive the treatment in the public institutions, in this cohort there were more patients came from private institutions. The most common symptom reported at diagnosis was associated with bone disease and the majority of the patients presented advanced disease (ISS 3 = 44%). Only 32% was considered non-eligible for ASCT at diagnosis. It is worth noting that most of the patients did not present any genetic alterations, which may impact in the identification of higher risk disease.

Comorbidity characteristics of multiple myeloma patients diagnosed in Finland 2005–2016

Multiple myeloma (MM) patients are predominantly elderly with comorbidities that have an impact on patient mortality and treatment decisions. We previously reported the patient characteristics and overall survival outcomes of the Finnish MM cohort diagnosed between 2005 and 2016 in a nationwide retrospective registry study comprising 3,851 adults. Here, we report detailed comorbidity characteristics for this real-world Finnish MM population at cohort entry and during follow-up. Data on diagnoses and causes of death were obtained from Finnish healthcare data registries and interrogated using various multistate time-to-event models. In the year preceding MM diagnosis, comorbidities (as per Charlson Comorbidity Index definition) were recorded in 38.0% of the cohort, of which 27.9% presented with pre-existing cardiovascular disease (CVD) and 4.8% had suffered a major adverse cardiac event (MACE). At 2 years post-MM diagnosis, cumulative incidence for CVD and MACE more than doubled to 57.1% and 11.4%, respectively, and only 31.9% of the cohort remained CVD-free. Prevalent secondary malignancies were recorded in 16.8% of the patient population at MM diagnosis, with cumulative incidence increasing steadily to 27.5% at 2 years and 33% at 5 years post-diagnosis. The main cause of mortality attributed to MM, CVD, secondary malignancy, or other causes remained stable throughout the follow-up, at an average of 74.2%, 9.4%, 9.8%, and 6.5%, respectively. Prevalence of CVDs and secondary malignancies is high in Finnish patients at MM diagnosis, with older male patients suffering from higher MACE and mortality risk. Proper recording and management of comorbidities alongside novel treatments remain crucial for optimal MM management.

Circulating miR-448 acts as a potential diagnostic biomarker for multiple myeloma

ABSTRACT Objective The current diagnostic methods for multiple myeloma (MM) include bone marrow aspiration and biopsy, which are not only complicated but also invasive, causing great pain to patients. Micro ribonucleotides (miRNA) exist stably in circulating plasma and could be easily detected, making them promising specific diagnostic markers for MM. Methods The expression of plasma miR-448 in MM patients was detected by real-time quantitative PCR analysis. Spearman correlation was used to analyze correlations between miR-448 expression and various clinic pathological characteristics of MM patients. The ROC and the AUC (95% confidence interval) were exploited to evaluate the potential of miR-448 acting as a diagnostic marker for MM patients. Results and discussion In this study, we found that the expression level of miR-448 in patients with MM was significantly higher than that in normal people and showed statistically differential expression in different stages of MM. Besides, we observed that the abundance of miR-448 in the plasma of newly diagnosed MM patients was positively correlated with the proportion of plasma cells (PC) in the bone marrow and the concentration of serum M protein (MP), respectively. In addition, ROC analysis demonstrated the sensitivity and specificity of the diagnostic value of miR-448 for MM are 92.90% and 87.50%, respectively. Conclusion Taken together, these results indicated that miR-448 may serve as a potential molecular diagnostic marker for MM.

Clinical Characteristics of Multiple Myeloma Patients with Early Relapse

To analyze the clinical characteristics of multiple myeloma(MM) patients with early relapse. A total of 50 MM patients with early relapse (≤12 months) and 50 matched controls with late relapse (>12 months) were selected. The time from diagnosis to relapse and related clinical data of the 100 patients were retrospectively analyzed, and the factors associated with early relapse were identified. Kaplan-Meier curve was used to analyze the overall survival (OS) time of the whole cohort. Area under the curve (AUC) was used to evaluate the effect of circulating plasma cells on early recurrence of the patients. The results showed that high-risk cytogenetics (FISH) (P=0.005), and ISS stage III (P=0.008) were associated with early recurrence of the patients. For patients with early relapse, high-risk FISH showed poor survival. Compared with the patients with late relapse, most of the chromosome karyotype of patients with early relapse showed quantitative and structural abnormalities. The expression of circulating plasma cells was significantly increased in patients with early recurrence group (P=0.0318). The response to initial treatment was poor in the early recurrence group (P=0.001), and the prognosis was significantly worse than those in the late recurrence group (median OS: 38 vs 81 months, P=0.002). Early relapse is a marker poor prognostic in MM patients, and such patients should be focused on the improving their prognosis.

Single-Center Real-World Experience of Multiple Myeloma in the 21st Century

Background/Aims: The incidence of multiple myeloma (MM) in Korea is rapidly increasing. The diagnostic criteria of MM have been updated and novel therapeutic agents are available. This study explored the features of MM patients registered at Asan Medical Center (AMC) and the outcomes over the past 15 years.Methods: Data were obtained from the AMC MM registry, which has been collecting the data of MM patients prospectively. The 774 MM patients included in our analysis were diagnosed from 2003, when thalidomide became available as a novel therapeutic agent, until April 2019. The 2-year survival rate of these patients was assessed. Patients were divided into two groups based on whether they were older or younger than 65 years, which is the cutoff age for the indication of autologous stem cell transplantation. Patients were also grouped according to the year of diagnosis: up to 2006, when bortezomib became available, and up to 2010, when the cost of lenalidomide was reimbursed.Results: Patients &lt; 65 years of age had better prognostic features, including a better performance, less advanced disease stage, and fewer abnormalities in their fluorescent in-situ hybridization (FISH) analysis results. A comparison of our Korean patients with patients registered in the Myeloma Related Disorder Registry data of Australia and New Zealand, showed ethnic discrepancies. The median overall survival of all patients was 3.7 years, with a 5-year survival rate of 41.8% and a 10-year survival rate of 23.4%. Survival progressively improved in patients diagnosed later. Age, performance status, renal function, C-reactive protein level, lactate dehydrogenase level, and cytogenetic findings were identified as significant prognostic factors.Conclusions: This real-world survey revealed the clinical features and survival rates of patients at a tertiary Korean Hospital who were diagnosed with MM at the beginning of 21st century.

A new prediction model integrated serum lipid profile for patients with multiple myeloma.

Purpose: This study aimed to explore a predictive risk-stratification model combing clinical characteristics and lipid profiles in multiple myeloma (MM) patients.Methods: The data of 275 patients in Sun Yat-Sen University Cancer Center were retrospectively analyzed and randomly divided into the training (n = 138) and validation (n=137) cohorts. Triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), Apolipoprotein B (Apo B) and Apo B/Apolipoprotein A1 (Apo A1) ratio were the prognostic factors identified through univariate and multivariate Cox analysis.Results: A 6-prognostic factor model was constructed based on Lasso regression. Patients were divided into low- and high-risk groups and the former group showed longer overall survival (OS) time (p<0.05). The area under the curve (AUC) of the risk score model for 5-and 10-year OS were 0.756 [95% CI: 0.661-0.850] and 0.940 [95% CI: 0.883-0.997], which exhibited better accuracy than International Staging System (ISS) and Durie and Salmon (DS) stage.Conclusion: This study aims to combine the lipid metabolism profile with the clinical characteristics of MM patients to generate a prognostic model. The nomogram integrating ISS stage and risk score increased the prediction accuracy. This model can monitor lipid profile as a simple and effective method, which has certain clinical significance for improving the accuracy of the prognosis and exploring potential therapeutic targets.

Assessment of Bone Marrow Biopsy and Cytogenetic Findings in Patients with Multiple Myeloma

Objective:Multiple myeloma (MM) is a malignant condition characterized by the accumulation of malignant plasma cells. Although MM remains incurable, the survival of MM patients has improved considerably due to the application of autologous stem cell transplantation, novel agents, and advanced treatment strategies. This study aimed to determine the cytogenetic characterization and bone marrow (BM) features of Turkish patients with MM.Materials and Methods:Eighty-five MM patients were admitted to Dokuz Eylül University Hospital in Turkey. BM samples of these MM patients were subjected to cytogenetic analyses at diagnosis and during therapy as a part of therapeutical and clinical evaluation. A complete cytogenetic study was performed using the G-banding technique. Fluorescence in situ hybridization (FISH) analysis was performed using cytoplasmic immunoglobulin. The degree of BM fibrosis was determined using reticulin histochemical staining. We determined the percentage of BM plasma cells based on the extent of CD38 staining.Results:Eighty-five MM patients were retrospectively identified between 2015 and 2021. The median age was 63 (38-90) years. Of the 85 patients, 60 (70.6%) were male and 25 (29.4%) were female. Seventy-two (84.7%) cases had BM fibrosis at the time of diagnosis. The most common was grade 2 fibrosis, recorded in 35 cases (41.2%). About 72.9% of the patients showed more than 50% plasma cells. FISH analysis indicated the presence of abnormal chromosomes in 37% (32/85) of the patients. The most frequent abnormality was Immunoglobulin heavy-chain (IGH) translocation (21.3%).Conclusion:Subgroup analysis of IGH mutations is crucial in the identification of high-risk MM patients. We believe that our study will contribute to the determination of BM biopsy and cytogenetic features of MM patients in our country.

Identification of a Novel Drug Sensitivity Biomarker Neuregulin-2 for Venetoclax in Non-t(11;14) Multiple Myeloma

Multiple myeloma (MM) is a malignant hematological cancer of plasma cells origin. However, MM with/without t(11;14) exists a huge therapeutic venetoclax response gap.To explore the clinical and genetic characteristics of MM patients, we divided the patients into two groups according to the t(11;14) translocation status. A total of 110 patients were enrolled in this analysis and 28 of them had t(11;14) translocation, of which 24 cases were MM patients and 4 cases were smoldering myeloma (SMM) patients. Compared to those t(11;14) counterparts, patients without t(11;14) has a higher ratio of early/later relapse, double/triple hit risk, higher mutation count as well as more hyper-karyotypes and other chromosome alterations (Figure 1A). Circos diagram analysis indicated the correlation between t(11;14) and most of cytogenetic alterations except del IGH, del 13q, t(6;14) and t(4;14),. To be specific, the strong connection between t(11;14) and Cyclin D was also in consistent with other reports (Figure 1B). With the normalized data of area under the curve (AUC), we further analyzed the drug sensitivity of patients with/without t(11;14) and 6 out of 76 drugs were identified to be significantly different. Compared to non-t(11;14), t(11;14) patients were significantly more sensitive to venetoclax as the lower AUC suggests. However, no significant difference in AUC of other potential myeloma drugs was found between the two groups (Figure 1C).In order to identify the critical genes associated with venetoclax sensitivity, we screened out the differentially expressed genes (DEGs) and applied weighted gene co-expression network analysis as previously described (Figure 1D and E). We combined clinical phenotype with the significant modules, and the key genes were screened based on the thresholds with cor. gene module membership > 0.5 and cor. gene significance > 0.3. Five modules were identified and of them brown and yellow modules showed significant negative correlations with AUC, with correlations being -0.4 and -0.31(p=0.01 and 0.07), respectively (Figure 1F). Furthermore, we analyzed these two modules in detail and finally screened 29 key genes associated with venetoclax sensitivity (Figure 1G), which were enriched in regulation of immune effector process pathway by Metascape, suggesting the immune dysfunction in these patients (Figure 1H).To identify the critical molecules affected by venetoclax, we analyzed the DEGs between the two groups divided by the median AUC value . In total, 143 genes were significantly upregulated and 38 genes downregulated in the high AUC group (i.e. low sensitivity to venetoclax) group . Next, we systematically analyzed the DEGs in brown module, AUC of venetoclax and of t(11;14). Notably, only NRG2 was identified to be involved in all these three aspects. NRG2, which presented a high sensitivity of venetoclax, was also validated to be more expressed in non-t(11;14) patients.Moreover, we could observe a trend of the expression of NRG2 increasing with the progression of myeloma, especially the significantly higher expression in disease stage of MM (P=0.0245) compared to sMM. In addition, NRG2 expression in myeloma is rather high compared to most hematological malignancies, while the extremely low expression was observed in AML which might correspond to its better reactivity to venetoclax. The expression of NRG2 in non-t(11;14) MM cells such as NCIH929, U266B1 and MM.1S was much higher than that in KMS12.BCL-2 expression was an important biomarker of venetoclax sensitivity. We found that NRG2 and BCL-2 had a strong positive correlation in non-t(11;14) MM patients (R 2=0.5016, P<0.001), while not correlated in patients with t(11;14) (R 2=0.08789, P=0.3034). Based on these results, we wondered whether the high expression of NRG2 in non-t(11;14) MM was associated with resistance of venetoclax. To validate our hypothesis, we knocked down NRG2 in MM.1S cells by lentivirus-mediated shRNA infection. The effective cells were screened out by puromycin or BFP and the knock-down efficiency was examined by qPCR as previously described. We found that the IC50 of venetoclax was much lower in MM.1S cells transfected with NRG2 shRNA than that of cells transfected with scramble shRNA, which suggested the increased sensitivity to venetoclax after NRG2 knockdown in non-t(11;14) MM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.