Clinical Lymphoma, Myeloma & Leukemia最新文献

{"title":"Second Primary Malignancies and Disease Transformation in Patients With Symptomatic Waldenström's Macroglobulinemia.","authors":"Maria Gavriatopoulou, Ioannis Ntanasis-Stathopoulos, Vasiliki Spiliopoulou, Charalampos Filippatos, Marie Christine Kyrtsonis, Nikolaos Giannakoulas, Emmanouil Spanoudakis, Sosanna Delimpasi, Michalis Michael, Stavroula Giannouli, Georgia Kaiafa, Eirini Katodritou, Evangelos Terpos, Meletios-Athanasios Dimopoulos, Efstathios Kastritis","doi":"10.1016/j.clml.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.007","url":null,"abstract":"<p><strong>Background: </strong>Waldenstrom macroglobulinemia (WM) is an indolent lymphoma with a long course; advanced age and immunosuppressive treatments may predispose for second primary malignancies (SPM).</p><p><strong>Methods: </strong>Consecutive symptomatic, newly diagnosed patients with WM who were diagnosed, treated and followed-up until May 28, 2024 were included in this study.</p><p><strong>Results: </strong>677 symptomatic patients with WM were included in the analysis; their median age was 69 years (range 24-93) and 209 were females (30.9%). Over a median follow-up of 5.32 years (range 0.01-25.61), 58 patients (8.6%) were diagnosed with a SPM. The median time from WM diagnosis to SPM diagnosis was 4.93 years (range 0.07-20.71). The incidence rate (IR) of a SPM per person-year was 0.009, translating to roughly 1 case per 100 person-years. The cumulative incidence (CI) of SPMs, accounting for death due to WM or other causes as a competing event, at 5 and 10 years was 4.0% and 7.2%. Furthermore, 23 patients (3.4%) developed transformation to high grade lymphoma. The median time from WM diagnosis to transformation was 5.36 years (range 0.01-25.6). The IR of transformation per person-year was 0.003, translating to 3 cases per 1000 person-years. The CI of transformation to high-grade lymphoma, accounting for death due to WM or other causes as a competing event, at 5 and 10 years, was 2.1% and 3.4%.</p><p><strong>Conclusions: </strong>Data from our prospectively maintained multicenter database revealed that 8.6% and 3.4% of symptomatic patients with WM developed a SPM and disease transformation, respectively, over a median follow-up of 5.3 years.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Increasing the Risk of Infection in Patients With Multiple Myeloma: From Biology to Prevention.","authors":"Cristina Encinas, Maria Jesús Blanchard, Rafael Alonso Fernández, José-Ángel Hernández-Rivas, Rafael Ríos Tamayo, Marina Machado-Vílchez, Joaquín Martínez-López, María Victoria Mateos","doi":"10.1016/j.clml.2025.06.012","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.012","url":null,"abstract":"<p><p>New therapies for multiple myeloma (MM) have improved survival rates but also increased infection risks, particularly during the early treatment of newly diagnosed disease (NDMM) and in cases of relapsed/refractory disease (RRMM). Understanding the factors contributing to Grade ≥3 infections in MM patients and identifying risk factors is critical for implementing effective prevention strategies and reducing infection incidence and severity. These factors can vary based on the disease, the patient's condition, and the anti-MM therapies employed. This review compiles and analyzes the key factors associated with the increased infection risk in MM patients, emphasizing infection rates linked to different treatment regimens and the reasons behind this increased risk. Additionally, it explores whether infection patterns differ according to the types of regimens or treatments used. Clinical trials report an infection risk of approximately 10% to 15% in ND patients with regimens combining immunomodulators (IMiDs), proteasome inhibitors (PIs), and corticosteroids. However, this risk rises above 30% when anti-CD38 monoclonal antibodies-now a cornerstone of MM treatment-are included. For triple-exposed RRMM patients receiving cellular therapies targeting BCMA, the infection risk exceeds 50%. In recent years, predictive models have been developed to assess the risk of Grade ≥ 3 infections in MM patients, enabling the optimization of preventive strategies. Furthermore, expert recommendations have been published to mitigate the incidence and severity of infections in this population. This review consolidates these recommendations and suggests strategies for managing infections in MM patients undergoing treatment.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Can Be Treated With Chemotherapy-Free Regimens Without Transplant.","authors":"Fadi G Haddad, Hagop Kantarjian, Jayastu Senapati, Nitin Jain, Nicholas J Short, Elias Jabbour","doi":"10.1016/j.clml.2025.06.019","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.019","url":null,"abstract":"<p><p>The incorporation of ponatinib into the frontline regimens of Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) deepened the molecular responses and improved outcomes. Patients with Ph-positive ALL who achieve a complete molecular response (CMR, undetectable BCR::ABL1 transcripts by RT-PCR) by 3 months of therapy have a better survival compared to those with persistent disease. Studies showed that the next-generation sequencing (NGS) assay, with a sensitivity up to 1 × 10^-6, is more sensitive than RT-PCR for the detection of measurable residual disease (MRD) in Ph-positive ALL and therefore carries a better prognostic value. Patients who achieve a 3-month CMR and undetectable MRD by NGS have excellent outcomes and may not need consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. However, omitting HSCT in certain patients with high-risk disease features, such as IKZF1^plus, remains to be determined. Outcomes were significantly improved with the combination of blinatumomab and ponatinib. This chemotherapy-free regimen resulted in a CMR rate of 80% by RT-PCR and 99% by NGS, with a 3-year overall survival rate of 89%. Only 2 of 76 patients (3%) underwent HSCT in this study. Combinations of newer TKIs (such as asciminib or olverembatinib) with blinatumomab (intravenous, subcutaneous) might further improve outcomes and are being explored. Achieving durable NGS MRD negativity can identify patients at low risk of relapse who might be candidates for treatment discontinuation. In this review, we discuss the current progress in the management of Ph-positive ALL, particularly the role of chemotherapy-free regimens in mitigating the need for HSCT.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence on Outcomes and Safety of Ropeginterferon Alfa-2b in Patients With Myeloproliferative Neoplasms: A Retrospective Cohort Study.","authors":"Yu-Sung Chang, Chieh-Yu Liu, Yu-Wen Chen, Sheng-Hsuan Huang, Hsing-Yu Lin, Chien-Chin Lin, Xavier Cheng-Hong Tsai, Feng-Ming Tien, Chieh-Lung Cheng, Chang-Tsu Yuan, Yuan-Yeh Kuo, Bor-Sheng Ko, Ming Yao, Hwei-Fang Tien, Wen-Chien Chou, Hsin-An Hou","doi":"10.1016/j.clml.2025.06.011","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.011","url":null,"abstract":"<p><strong>Background: </strong>Ropeginterferon alfa-2b-njft (ropegIFN) has demonstrated superior efficacy over hydroxyurea in polycythemia vera (PV); however, real-world data on its application across Philadelphia chromosome-negative (Ph-) myeloproliferative neoplasms (MPNs) remain limited.</p><p><strong>Patients and methods: </strong>This retrospective cohort study included 64 patients with Ph- MPNs (15 PV, 16 essential thrombocythemia [ET], 5 prefibrotic myelofibrosis [preMF], and 28 with overt myelofibrosis [MF]) treated with ropegIFN between October 2018 and June 2024.</p><p><strong>Results: </strong>After a median follow-up of 5.3 years, the hematological response (HR) rates at 36 months were 87% in PV, 75% in ET, 80% in preMF, and 45% in overt MF (P = .026). Best molecular response (MR) rates were 80% in PV, 69% in ET, 75% in preMF, and 47% in overt MF (P = .11). The median JAK2 variant allele frequency (VAF) declined significantly from 67.9% at baseline to 18.7% during follow-up (P < .001), with consistent reductions across MPN subtypes confirmed by GEE analysis. In patients with MF, neither HR nor MR was observed among those harboring high-molecular-risk (HMR) mutations (24-month HR: 0% vs. 72%; P = .002; 24-month MR: 0% vs. 18%; P = .4). Additionally, these patients exhibited a significantly higher cumulative incidence of adverse events (48% vs. 7%; P < .001).</p><p><strong>Conclusions: </strong>RopegIFN demonstrated hematological and molecular efficacy across Ph- MPN subtypes and was generally well tolerated. However, its effectiveness appears limited in patients with MF, particularly those with high-molecular-risk (HMR) mutations. These findings support the potential disease-modifying role of ropegIFN and highlight the need for prospective multicenter studies to validate its long-term impact on disease progression and survival.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"R-DA-EPOCH Versus DA-EPOCH-R: Impact of Chemoimmunotherapy Sequencing on Treatment Outcomes in Patients With Diffuse Large B-Cell Lymphoma.","authors":"Benjamin J Lee, Shawn P Griffin, Jean Doh, Anthony Quach, Yujiao Sun, Elizabeth A Brem, Richard A Van Etten, Edward L Nelson, Catherine C Coombs, Alexandre Chan","doi":"10.1016/j.clml.2025.06.018","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.018","url":null,"abstract":"<p><strong>Background: </strong>Chemoimmunotherapy with rituximab (R) added to dose-adjusted (DA)-EPOCH (continuous infusion of etoposide, vincristine, and doxorubicin with cyclophosphamide and prednisone) has become a standard treatment approach for high-risk diffuse large B-cell lymphoma (DLBCL) patients. In contrast to pivotal trials that sequenced rituximab with the initiation of each chemoimmunotherapy cycle, our institution adopted delaying rituximab following discharge after EPOCH completion in patients requiring inpatient chemotherapy (DA-EPOCH-R). Herein, we evaluate the efficacy and safety of rituximab sequencing with EPOCH initiation and after EPOCH administration.</p><p><strong>Patients and methods: </strong>A retrospective chart review of all DLBCL patients who received first-line treatment with R-DA-EPOCH or DA-EPOCH-R between 2016 and 2023 was conducted. Outcomes of interest included progression-free survival (PFS), overall response rate (ORR), complete response (CR), overall survival (OS), and cumulative incidence of relapse.</p><p><strong>Results: </strong>A total of 31 DA-EPOCH-R and 35 R-DA-EPOCH patients were included. PFS at 4-years was not significantly different between DA-EPOCH-R and R-DA-EPOCH treated patients (75.2% vs. 77.9%; HR 1.10; 95% CI, 0.38-3.13; P = .86). ORR (93.5% vs. 100%; P = .22) and CR (90.3% vs. 85.7%; P = .71) were also similar between cohorts. Rituximab-related infusion reactions were higher among R-DA-EPOCH-treated patients with cycle 1 (P = .038).</p><p><strong>Conclusion: </strong>Our findings suggest delaying rituximab following EPOCH did not affect treatment outcomes and are associated with lower infusion reactions.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of Sequential BCMA-directed therapies in Relapsed Refractory Multiple Myeloma After Belantamab Exposure.","authors":"Prerna Mewawalla, Rachel Dileo, Yue Yin, Christopher Strouse, Hira Shaikh, James A Davis, Omar Alkharabsheh, Aliya Rashid, Nausheen Ahmed, Al-Ola Abdallah, Hamza Hashmi","doi":"10.1016/j.clml.2025.06.015","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.015","url":null,"abstract":"<p><strong>Background: </strong>While B-cell maturation antigen (BCMA) directed therapies are increasingly utilized for multiple myeloma, outcomes with sequential treatments with BCMA-directed therapies remain an area of active investigation.</p><p><strong>Methods: </strong>In this multicenter retrospective analysis, we evaluated the real-world outcomes of patients treated with BCMA-directed therapies including CAR T and bispecific antibody (BsAb) following progression on the antibody-drug conjugate belantamab mafodotin. A total of 23 patients (14 CAR T, 9 BsAb) were included in the analysis.</p><p><strong>Results: </strong>The median patient age was 68 (range 37-82) years, with 43% having high-risk cytogenetics, 87% having received ≥4 prior lines of therapy, and 35% with extramedullary disease at the time of treatment. The overall response rate (ORR) for the entire population was 65%, 44% in the BsAb and 79% in the CAR T subgroup. With a median follow-up of 24 months, median progression-free survival (PFS) and overall survival (OS) were 5 (range 2-10) months and 28 (range 16-NR) months, respectively. There was no difference in median PFS between patients who received a BsAb vs CAR T (p=0.8), or based on time from belantamab to BCMA therapy (<6 months vs ≥6 months, p=0.8).</p><p><strong>Conclusion: </strong>Treatment with BCMA-directed BsAb or CAR T remains feasible for RRMM patients after progression on belantamab. However, outcomes remain inferior compared to those without prior BCMA exposure and were not affected by choice of therapy or time since last BCMA exposure.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SOHO State of the Art Updates and Next Questions | The Optimal Management of Waldenström Macroglobulinemia.","authors":"Alberto Guijosa, Alicia de Las Heras, Shayna Sarosiek, Jorge J Castillo","doi":"10.1016/j.clml.2025.06.017","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.017","url":null,"abstract":"<p><p>Waldenström macroglobulinemia (WM) is a rare IgM-secreting lymphoplasmacytic lymphoma with recurrent somatic mutations in MYD88 and CXCR4 observed in the malignant cells of >90% and 30% to 40% of the patients. Given its rarity, WM poses specific diagnostic and management challenges. The diagnosis of WM is clinicopathological and no pathognomonic findings exist. The combination of a monoclonal IgM paraproteinemia, lymphoplasmacytic lymphoma in the bone marrow or other organs, and the MYD88 L265P mutation makes a diagnosis of WM with a high specificity. Approximately, a third of the patients will be asymptomatic at diagnosis and the best approach is to observe, as these patients have similar survival rates than age, sex and year of diagnosis-matched individuals of the general population. Eighty percent of patients diagnosed with asymptomatic WM will need treatment within 10 years. Treatment is indicated in symptomatic patients in whom the symptoms affect the patients' activities and are likely to be caused by the disease process. Multiple standard treatment options are safe and effective in symptomatic patients, including rituximab in combination with alkylating agents or proteasome inhibitors, covalent BTK inhibitors, and BCL2 antagonists. Noncovalent BTK inhibitors have emerged as a novel treatment option. Second-generation BCL2 antagonists, BTK degraders, antibody-drug conjugates and bispecific T-cell engagers are being evaluated in clinical trials. Multinational collaborative consortia to accelerate clinical trial design and execution in WM have emerged in Europe and the United States.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Patient Demographics and Smoldering Multiple Myeloma Progression to Multiple Myeloma: A SEER-Medicare Data Analysis.","authors":"Poy Theprungsirikul, Rong Wang, Ishfaq Ahmad, Natalia Neparidze, Xiaomei Ma, Su-Hsin Chang, Shi-Yi Wang","doi":"10.1016/j.clml.2025.06.016","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.016","url":null,"abstract":"<p><strong>Background: </strong>While several risk stratification models for smoldering multiple myeloma (SMM) to symptomatic multiple myeloma (MM) progression have been developed, the association between patient demographics, such as race, gender, and age, and SMM progression is not well understood.</p><p><strong>Methods: </strong>Analyzing surveillance, epidemiology, and end results (SEER)-Medicare data, we applied a previously developed algorithm to identify patients with SMM diagnosed between 2007 and 2019. We used noncancer patients from the 5% random sample of Medicare beneficiaries as the controls. Cox proportional hazards models were applied to assess the association between race/gender/age and the development of hypercalcemia, renal failure, anemia and bone disease among SMM patients and the controls. We applied bootstrapping to calculate the estimates hazard ratios (aHRs) and 95% confidence intervals (CIs) of progression among SMM patients, adjusting for that of the noncancer controls.</p><p><strong>Results: </strong>Out of 1235 identified SMM patients (median age 75 years, White 76.7%), 856 (69.3%) of them progressed to symptomatic MM. Race (Black vs. White aHR = 0.82, 95% CI: 0.65-1.01) and gender (male vs. female aHR = 0.99, 95% CI: 0.86-1.13) were not significantly associated with SMM progression. Only age was negatively associated with SMM progression (75-79 years vs. 66-69 years aHR = 0.71, 95% CI: 0.58-0.87; 80-84 years vs. 66-69 years aHR = 0.59; 95% CI: 0.46-0.74; and ≥ 85 years vs. 66-69 years aHR = 0.59; 95% CI: 0.45-0.75).</p><p><strong>Conclusion: </strong>This analysis provided insight into important parameters for MM natural history modeling by demonstrating that only age, but not race and gender, is negatively associated with SMM progression.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence and Burden of Lower-Risk Myelodysplastic Syndrome: A Nationwide Population Study.","authors":"Maud D'Aveni, Jérôme Fernandes, Mélanie Chartier, François-Emery Cotté, Nicolas Pagès, Arnaud Panes, Aurélie Schmidt, Léa Webert, Thibault Comont","doi":"10.1016/j.clml.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.009","url":null,"abstract":"<p><strong>Background: </strong>Myelodysplastic syndromes (MDS) are hematological malignancies that primarily affect older individuals, often leading to anemia, which significantly impacts quality of life. Until now, the management of lower-risk MDS (LR-MDS) typically includes erythropoiesis-stimulating agents (ESAs) as first-line treatment, with transfusions becoming necessary in cases of ESA resistance. This study aimed to assess the incidence, prevalence, and clinical outcomes of LR-MDS patients in France, using the French National Health Data System (SNDS).</p><p><strong>Materials and methods: </strong>A retrospective cohort of 822 LR-MDS patients treated between 2018 and 2022 was analyzed, with patients classified based on transfusion dependency.</p><p><strong>Results: </strong>Results showed a median LR-MDS extrapolated incidence of 5,850 patients per year in France (between 6.9 to 9.3 cases per 100,000 persons). Transfusion-dependent (TD) patients represented 32.5% of the cohort. TD patients had a significantly lower 2-year overall survival rate of 53% compared to 70% in nontransfusion-dependent (NTD) patients. Over the study period, 41.9% (N = 112) died out of 267 newly treated LR-MDS patients. Also, there were 88 events of death (with no progression), 26 estimated progression to HR-MDS and 11 progression to acute myeloid leukemia.</p><p><strong>Conclusion: </strong>These findings highlight the substantial burden of transfusion dependency in LR-MDS patients, emphasizing the need for improved therapeutic strategies.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Proteomic Profiles Among White and African American Individuals With Monoclonal Gammopathy of Unknown Significance (MGUS) and Multiple Myeloma (MM).","authors":"Cindy Varga, Kip D Zimmerman, David M Foureau, Sumaiya A Nazli, Peter M Voorhees, Shebli Atrash, Barry Paul, Christopher Ferreri, Michael Olivier, Manisha Bhutani","doi":"10.1016/j.clml.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.clml.2025.06.008","url":null,"abstract":"<p><strong>Background: </strong>Compared to Non-Hispanic Whites, African American (AA) individuals have a 2-fold higher incidence of MGUS and MM. Understanding the molecular mechanisms that drive progression from MGUS to MM is crucial, but few studies have explored whether there are differences in protein expression patterns in the progression of MGUS to MM by race. Here, we used mass-spectrometry to compare proteomic profiles between AA and White individuals with MGUS and MM. We hypothesized that biological differences between MGUS and MM could be captured by measuring protein presence and abundance. The primary aim was to identify protein pathways distinguishing these 2 stages.</p><p><strong>Methods: </strong>In this study, we conducted untargeted serum protein profiling using data-independent acquisition mass spectrometry proteomics, quantifying over 1550 proteins in 30 MGUS and 30 newly diagnosed, treatment-naive MM samples. Samples were evenly split by self-reported race and matched for age and sex. Linear and logistic regression models were used to test for association between protein abundance or presence and MGUS/ MM status, adjusting for sex, age, BMI, batch, and race as covariates. Missing values in logistic regression were imputed as 0, with all other values set to 1. Proteins with unadjusted P < .05 were selected for pathway and network analysis.</p><p><strong>Results: </strong>No significant differences were observed between AA and White patients with MM in M-spike level (P = .644), light chain involvement (P = .122), or plasmacytosis (P = .877). Proteomic analysis identified 26 proteins that significantly differed in detection or in abundance between MGUS and MM samples in a race agnostic manner (P < .05), with 15 showing increased abundance in MM and 11 varying in detection rates (presence or absence). Among these, ICAM-3, HSP90B1, ORM2, MAN1A1, OSCAR, PRKDC, and cDNA-FLJ-41552 (interaction P < .05) were particularly notable. Two proteins, PRKDC and cDNA FLJ41552 were decreased exclusively in AA patients with MM (interaction P < .05), suggesting population specific differences. Notably, 16 proteins showed changes between MGUS and MM exclusively in White patients (interaction P < .05), with the most significant being SERPIND1, C4B, CPN1, CNDP1 in abundance, and SERPINE1, CA2, CD109 in detection.</p><p><strong>Conclusion: </strong>While the exact roles of these molecular pathways in the progression from MGUS to MM remain unclear, the identified protein differences may serve as biomarkers and therapeutic targets, warranting further validation and functional studies for clinical application. In addition, the differential expression of PRKDC in AA patients suggests potential population-specific vulnerabilities. Validation of these findings in additional cohorts will help assess the potential usefulness of these biomarkers in predicting transition from MGUS to MM.</p>","PeriodicalId":10348,"journal":{"name":"Clinical Lymphoma, Myeloma & Leukemia","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}