[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

[Guideline for the diagnosis and management of multiple myeloma-related renal impairment (2024 version)].

Renal impairment is a common complication of multiple myeloma (MM). All patients with MM should be assessed for the presence and severity of renal impairment. The clinicopathological manifestations of MM-related renal impairment are diverse and complex; accordingly, except for light-chain nephropathy, which can often be diagnosed without biopsy based solely on clinical criteria, a renal biopsy is needed for an accurate diagnosis. Supportive care, such as adequate hydration, is required for all patients with MM-related renal impairment. The guideline provide the principles for dose adjustment of the drugs used for MM with renal impairment, including proteasome inhibitors, immunomodulators, monoclonal antibodies, small molecule inhibitors, and alkylating agents, as well as those used for myeloma bone disease. Autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell immunotherapy (CAR-T) are effective in patients with moderate renal impairment and are tolerated by the patients. The Chinese Hematology Association; the Chinese Geriatrics Association, Society of Hematology; and the Chinese Research Hospital Association, Society of Nephrology asked experts to collate information on current progress in clinical research relating to MM with renal impairment. This guideline was developed based on the gathered data combined with the latest international consensus and clinical practice guidelines.

Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma.

BACKGROUND: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. METHODS: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors. RESULTS: The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37-69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed "double hit" (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046-8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217-13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year. CONCLUSIONS: This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.

[Application of the Second Revision of the International Staging System (R2-ISS) in the prognostic assessment of newly diagnosed multiple myeloma].

Objective: To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed. Results: ①326 patients were included in the study, 190 of whom were males. The median age was 63 years, and the median followup time was 37 months. R2-ISS can effectively predict prognosis, particularly for R-ISS Ⅱ patients. The median progression-free survival (PFS) time of R2-ISS Ⅰ, R2-ISS Ⅱ, R2-ISS Ⅲ, and R2-ISS Ⅳ was 52, 29, 20, and 15 months (P<0.001), while the median overall survival (OS) time was 91, 60, 44, and 36 months (P<0.001). Multifactor analysis revealed that ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, LDH increased, and age >65 years old were independent negative prognostic factors for OS. ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, and LDH were independent negative prognostic factors for PFS. ②The C-index score of R2-ISS was 0.724, higher than that of R-ISS (0.678), indicating high prediction efficiency. ③The median PFS for 1q+-related double-hit in R2-ISS Ⅲ and Ⅳ were 20, 15 months (P=0.084) and the median OS were 35, 36 months (P=0.786), respectively. In R2-ISS Ⅲ, there were twenty-seven cases of 1q+-related double-hit, sixty-one cases of 1q+ single abnormality, and sixty-eight cases with no 1q+. The median PFS for the three groups were 20, 18, and 21 months (P=0.974), while the median OS was 35, 47, and 56 months (P=0.042), respectively. Adjusting the assignment of 1q+ to 1, the median PFS and OS of different R2-ISS stages differed significantly after regrouping (P<0.001) . Conclusions: The prognostic stratification value of R2-ISS is higher than R-ISS, particularly in the highly heterogeneous R-ISS Ⅱ population. Adjusting the assignment of the 1q+-related double-hit can improve R2-ISS, which should be validated in future studies with multi-center and expanded cases.

Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597). SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. LIMITATION: The prediction model will require external validation. CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.

Machine learning evaluation for identification of M-proteins in human serum.

Serum electrophoresis (SPEP) is a method used to analyze the distribution of the most important proteins in the blood. The major clinical question is the presence of monoclonal fraction(s) of antibodies (M-protein/paraprotein), which is essential for the diagnosis and follow-up of hematological diseases, such as multiple myeloma. Recent studies have shown that machine learning can be used to assess protein electrophoresis by, for example, examining protein glycan patterns to follow up tumor surgery. In this study we compared 26 different decision tree algorithms to identify the presence of M-proteins in human serum by using numerical data from serum protein capillary electrophoresis. For the automated detection and clustering of data, we used an anonymized data set consisting of 67,073 samples. We found five methods with superior ability to detect M-proteins: Extra Trees (ET), Random Forest (RF), Histogram Grading Boosting Regressor (HGBR), Light Gradient Boosting Method (LGBM), and Extreme Gradient Boosting (XGB). Additionally, we implemented a game theoretic approach to disclose which features in the data set that were indicative of the resulting M-protein diagnosis. The results verified the gamma globulin fraction and part of the beta globulin fraction as the most important features of the electrophoresis analysis, thereby further strengthening the reliability of our approach. Finally, we tested the algorithms for classifying the M-protein isotypes, where ET and XGB showed the best performance out of the five algorithms tested. Our results show that serum capillary electrophoresis combined with decision tree algorithms have great potential in the application of rapid and accurate identification of M-proteins. Moreover, these methods would be applicable for a variety of blood analyses, such as hemoglobinopathies, indicating a wide-range diagnostic use. However, for M-protein isotype classification, combining machine learning solutions for numerical data from capillary electrophoresis with gel electrophoresis image data would be most advantageous.

Megalosplenia as an initial manifestation of multiple myeloma with a novel CYLD gene mutation: A case report and literature review.

INTRODUCTION: Megalosplenia in newly diagnosed multiple myeloma (MM) is extremely rare, posing diagnostic and therapeutic challenges due to its unusual location and clinical manifestations and lack of optimal therapeutic strategies. CASE PRESENTATION: A 65-year-old female who was previously healthy presented with a history of ecchymosis on her right leg accompanied by progressive fatigue for 2 weeks. She was admitted to our center in July 2019 due to thrombocytopenia. The patient presented with megalosplenia, anemia, monoclonal protein (λ-light chain type) in the serum and urine, and 45.6% malignant plasma cells in the bone marrow. Splenectomy was performed due to persistent splenomegaly after 3 cycles of the bortezomib plus dexamethasone regimen, and immunohistochemistry results indicated λ-plasmacytoma of the spleen. The same cytogenetic and molecular abnormalities, including t(14;16), 14q32 amplification, 16q32 amplification, 20q12 amplification, and a novel CYLD gene mutation, were identified using fluorescence in situ hybridization and next-generation sequencing in both bone marrow and spleen samples. Therefore, a diagnosis of MM (λ-light chain type, DS III, ISS III, R-ISS III, high-risk) with spleen infiltration was proposed. The patient did not achieve remission after induction treatment with bortezomib plus lenalidomide and dexamethasone or salvage therapy with daratumumab plus ixazomib and dexamethasone. However, she ultimately did achieve very good partial remission with a regimen of bendamustine plus lenalidomide and dexamethasone. Unfortunately, she died of pneumonia associated with chemotherapy. CONCLUSION: To our knowledge, only 8 cases of spleen plasmacytoma at MM diagnosis have been described previously. Extramedullary myeloma patients with spleen involvement at diagnosis are younger and that the condition is usually accompanied by splenic rupture with aggressive clinical features and poor prognosis. Further studies are needed to explore pathogenesis and effective therapies to prolong the survival of such patients.

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.

There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.

Comparison of trace elements in peripheral blood and bone marrow of newly diagnosed multiple myeloma patients.

Trace elements are essential micronutrients for the human body. Their roles are indispensable, as they are involved in a wide range of vital biological processes. In this study, we aimed to evaluate alterations in trace elements in the blood and bone marrow serum of patients with newly diagnosed multiple myeloma (NMM). The levels of zinc (Zn), copper (Cu), iron (Fe), manganese (Mn), magnesium (Mg), selenium (Se), arsenic (As), boron (B), nickel (Ni), silicon (Si) and chromium (Cr) were analyzed in the venous blood samples of the patient group comprising 70 patients with NMM (41 males and 29 females) and compared to those in the control group comprising 30 individuals (18 males and 12 females). In addition, trace element levels were analyzed in bone marrow samples from the patient group. Blood and bone marrow serum levels were quantified using inductively coupled plasma optical emission spectrometry. When the blood samples of the patient and control groups were compared: Zn (p = 0.011), Fe (p = 0.008), Mn (p = 0.046), Se (p < 0.001), As (p < 0.001), Ni (p < 0.001) and Cr (p < 0.001) levels were significantly higher in the patient group than in the control group. Higher Zn, Fe, Mn, Se, As, Ni and Cr levels in the NMM patients suggest that alterations of trace elements could be predisposing factor that initiates the malignant process. The relationship between malignancies and trace elements is crucial for the development of adjuvant therapy strategies and preventive medicine and as biomarkers for cancer diagnosis. Therefore, there is a need for studies examining the relationship between hematological malignancies and trace elements.

[Consensus for the diagnosis and management of extramedullary plasmacytoma in China(2024)].

Extramedullary plasmacytoma (EMP) is a special type of malignant plasmacytosis, which is complex and heterogeneous. Most EMP patients have poor prognosis and lack a stratified prognostic system or ideal treatment strategy supported by evidence-based medical evidence, which cannot meet clinical needs. In order to improve the understanding of this disease entity, Plasma Cell Disease Group, Chinese Society of Hematology, Chinese Medical Association and Chinese Myeloma Committee-Chinese Hematology Association developed the "Chinese Expert Consensus on the diagnosis and treatment of extramedullary plasmacytoma", which aims to standardize the clinical diagnosis and treatment of EMP and ultimately improve the overall survival of patients with plasmacytoma.

Complex karyotype determined using conventional cytogenetic analysis is a poor prognostic factor in patients with multiple myeloma.

High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.

Recurrence of solitary plasmacytoma in the liver 10 years after the onset of multiple bone lesions.

A 79-year-old man presented with a history of solitary plasmacytoma in the bone 10 years ago. Chemoradiotherapy was effective, and remission was maintained with intermittent treatment at relapse of the bone lesions. One year after the last treatment, a follow-up computed tomography (CT) scan revealed multiple liver masses, and a liver biopsy revealed plasmacytoma. There was no clonal plasma cell infiltration in the bone marrow, and the final diagnosis was solitary plasmacytomas of the liver. Although liver involvement is known in relapsed refractory multiple myeloma, solitary plasmacytoma in the relapsed stage confined to the liver is rare, and all previous reports have been from the initial presentation. To the best of our knowledge, this is the first recurrent case of solitary plasmacytoma of the liver.

Smouldering multiple myeloma: To seek or not to seek? To treat or not to treat. That is the question.

In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence-based approach to managing these patients. Key questions remain yet unsolved. Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193-1206.

Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis.

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.

A rare case of daratumumab-associated encephalopathy in multiple myeloma.

Aim: Daratumumab, a CD38 monoclonal antibody, has been widely used in patients with multiple myeloma. Although a variety of adverse events have been reported, consciousness impairment has not been reported yet. We report a case of encephalopathy associated with daratumumab. Case presentation: A 57-year-old male, diagnosed with relapsed multiple myeloma, was treated with daratumumab. He developed a loss of consciousness after the first administration. Cerebral spinal fluid and magnetic resonance imaging of the brain suggested encephalopathy. Conclusion: It is recommended to be aware of rare but life threatening side effects of daratumumab. We present a case of rare encephalopathy characterized by consciousness disorder associated with daratumumab, which was successfully resolved on prompt institution of steroids, although the mechanism was unknown.

Daratumumab is a drug. It is used to treat multiple myeloma. Many patients use this drug. It has many side effects. But consciousness disorder is rare. A 57-year-old male was diagnosed with multiple myeloma. He was treated with daratumumab. He became unconscious after this treatment. Steroids helped his recovery.

Exploring Indicators of Vulnerability in Older Adults With Newly Diagnosed Multiple Myeloma.

New publication provides insights into the impact of disability on outcomes in older adults with multiple myeloma.

Progression free survival of myeloma patients who become IFE-negative correlates with the detection of residual monoclonal free light chain (FLC) by mass spectrometry.

Deeper responses are associated with improved survival in patients being treated for myeloma. However, the sensitivity of the current blood-based assays is limited. Historical studies suggested that normalisation of the serum free light chain (FLC) ratio in patients who were negative by immunofixation electrophoresis (IFE) was associated with improved outcomes. However, recently this has been called into question. Mass spectrometry (MS)-based FLC assessments may offer a superior methodology for the detection of monoclonal FLC due to greater sensitivity. To test this hypothesis, all available samples from patients who were IFE negative after treatment with carfilzomib and lenalidomide-based induction and autologous stem cell transplantation (ASCT) in the Myeloma XI trial underwent FLC-MS testing. FLC-MS response assessments from post-induction, day+100 post-ASCT and six months post-maintenance randomisation were compared to serum FLC assay results. Almost 40% of patients had discordant results and 28.7% of patients with a normal FLC ratio had residual monoclonal FLC detectable by FLC-MS. FLC-MS positivity was associated with reduced progression-free survival (PFS) but an abnormal FLC ratio was not. This study demonstrates that FLC-MS provides a superior methodology for the detection of residual monoclonal FLC with FLC-MS positivity identifying IFE-negative patients who are at higher risk of early progression.

Myelomatous pleural effusion in multiple myeloma- A rare presentation.

Multiple myeloma is a malignant plasma cell condition that mostly affects the skeletal system and bone marrow. Pleural effusions are uncommon and typically result from other conditions coexisting with multiple myeloma. Malignant myelomatous pleural effusions are rare complications of multiple myeloma, occurring in less than 1% of patients and are associated with poor prognosis having mean survival of less than 4 months. The present case report is a 41-year-old multiple myeloma patient who developed bilateral pleural effusion at a disease relapse. Chemotherapeutic regimen of cyclophosphamide, bortezomib, and dexamethasone given. Despite a positive response to treatment, the patient's condition worsened over the course of following month and he eventually passed away. Myelomatous pleural effusion indicates poor prognosis and early consideration helps in quick diagnosis and initiation of treatment which may help in improving prognosis.