Objective:To explore the correlation between body mass index (BMI) and the risk of multiple myeloma (MM).Methods:A two-sample Mendelian randomization (MR) analysis was utilized. The data were obtained from genome-wide association study (GWAS) datasets in the IEU OpenGWAS database. The dataset number for exposure factor BMI was ieu-a-2, involving 339 224 mixed populations (males and females) and containing 2 555 511 single nucleotide polymorphisms (SNP); the dataset number for outcome factor MM was ieu-b-4957, involving 372 617 European populations (601 MM patients and 372 016 healthy individuals), containing 8 615 746 SNP; the BMI and MM reference genomes were both HG19/GRCh37 provided by the Genetic Investigation of Anthropometric Traits (GIANT) collaborative organization. From dataset ieu-a-2, 79 SNP significantly associated with BMI were selected as instrumental variables ( F > 10), and then validated in the outcome factor dataset (ieu-b-4957), with missing SNP excluded, resulting in 76 retained instrumental variables. MR analyses were performed using the inverse variance weighted (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method. Sensitivity analyses were conducted using the Cochran Q test, MR-Egger regression intercept and leave-one-out approach. Results:IVW results showed a positive correlation between BMI and the risk of MM ( OR = 1.001, 95% CI: 1.000-1.002, P = 0.012), which was supported by the MR-Egger method ( OR = 1.003, 95% CI: 1.000-1.005, P = 0.022). The sensitivity analyses results showed that neither the MR-Egger intercept (intercept = -4.336×10 -5, P = 0.158) nor the heterogeneity test (IVW: Q = 82.02, P = 0.271) found significant heterogeneity or horizontal pleiotropy, indicating high robustness of the results. Conclusions:BMI may be a potential risk factor for the development of MM.

Mantle cell lymphoma (MCL) is a rare B-cell lymphoma characterized by both the incurable nature of indolent lymphomas and the clinical course of aggressive lymphomas. The integration of high-dose cytosine arabinoside (Ara-C) and autologous hematopoietic stem cell transplantation (ASCT) has led to substantial improvement in the outcomes of MCL patients in the immunochemotherapy era. More recently, the widespread use of small molecule targeted agents, particularly Bruton tyrosine kinase inhibitor (BTKi), has re-shaped the therapeutic landscape of MCL patients and challenged the traditional role of high-dose Ara-C and ASCT. Novel immunotherapies including bi-specific antibodies and chimeric antigen receptor T-cell (CAR-T) therapy have emerged as important treatment options for MCL patients with relapsed or refractory disease. With advances in multi-omics profiling, the development of personalized, potentially curative strategies based on individual genetic and immune features is expected to become a major focus of future research on MCL. This article will delve into the latest research progress in the treatment and genetics and translational research on MCL patients, focusing on the latest progress of research on the treatment of newly diagnosed MCL patients, treatment of relapsed/refractory MCL patients, and the genetics and translational treatment of MCL patients, and explore the evolution and future direction of its treatment model.
Humans ; Lymphoma, Mantle-Cell/immunology* ; Translational Research, Biomedical ; Hematopoietic Stem Cell Transplantation ; Immunotherapy

Circulating tumor cells (CTC) are tumor cells that are shed from primary or secondary lesions of tumors and enter the blood. Although multiple myeloma (MM) is characterized by malignant proliferation of plasma cells in the bone marrow, it is also a hematologic malignancy with a systemic distribution of tumor cells. Circulating multiple myeloma cells (CMMC) can be widely detected in MM patients and can represent the clonality and invasiveness of MM cells themselves. In recent years, with the continuous improvement of detection technology and the deepening of understanding, CTC detection has shown good clinical application prospects in the study of MM. This article reviews the research progress of isolation and identification of CMMC and its application in diagnosis and prognosis of MM.

Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Objective:To investigate the efficacy and adverse effects of combination therapy containing venetoclax in the treatment of t(11; 14) plasma cell disorders.Methods:A retrospective case series study was conducted. The clinical data of plasma cell disorders patients with t(11; 14) treated with combination therapy containing venetoclax in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 2020 to September 2023 were collected. The general data included baseline clinical characteristics, treatment regimens, treatment responses, survival, and adverse events. The duration of orally administered venetoclax-based treatment regimen was 28 d, and the dose of venetoclax was appropriately adjusted according to the tumor burden and general conditions of patients. Patients were grouped according to drug dosage and treatment regimen. The overall survival (OS) analysis was performed by using Kaplan-Meier method and log-rank test was used for comparison among groups.Results:Among the 14 plasma cell disorders patients with t(11;14), 13 had multiple myeloma (MM) and 1 had primary plasma cell leukemia (pPCL). The median time [ M ( Q1, Q3)] from initial diagnosis to venetoclax treatment was 21 months (8 months, 39 months). The median number of therapy lines was 2 (1, 4); 7 patients had drug resistance to both proteasome inhibitors (PI) and immunomodulators (IMiD), and 5 patients had drug resistance to PI, IMiD and anti-CD38 monoclonal antibodies; 2 patients died after 1 uncompleted course of treatment and they were not enrolled into efficacy evaluation and survival analysis. Among the 11 MM patients evaluable for treatment response, 6 achieved at least partial remission (PR). Of the 4 patients who received the first-line or second-line therapy containing venetoclax, 2 achieved strict complete remission (sCR), 1 achieved very good partial remission (VGPR), and 1 achieved PR. The median course number of therapy lines with venetoclax was 2 (2, 6), and the median acting time was 1.1 months (0.75 months, 1.75 months). Until the last follow-up in May 2024, the median duration of remission of 11 MM patients was 3.3 months (95% CI: 0-7.1 months), and the median OS time was 22.7 months (95% CI: 0-52.5 months). The median OS time was 9.6 months, 31.2 months, respectively in venetoclax combined with PI group (6 cases) and venetoclax combined with daratumumab (Dara) group (4 cases), and the difference in OS between the 2 groups was statistically significant ( P = 0.093); the median duration of remission was 1.7 months and 9.8 months, respectively in venetoclax combined with PI group and venetoclax combined with Dara group, and the difference was statistically significant between the 2 groups ( P = 0.025). The median OS time in high-dose group (maximum dose of venetoclax ≥300 mg, 6 cases) and low-dose group (maximum dose of venetoclax < 300 mg, 5 cases) was 31.2 and 7.5 months, respectively, and the difference in OS was statistically significant ( P = 0.013). The median duration of remission was 9.8 months, 1.6 months, respectively, and the difference was statistically significant ( P = 0.048). Grade ≥3 adverse events of 11 MM patients included neutropenia, lymphopenia, infection, thrombocytopenia, and hypokalemia; 6 patients experienced grade ≥3 adverse events, 2 patients discontinued treatment due to adverse events, and no treatment-related deaths occurred. The pPCL patient received 5 courses of treatment with venetoclax plus DECP (cisplatinum + etoposide + cyclophosphamide + dexamethasone) induction therapy followed by chimeric antigen receptor T cell therapy and then continued venetoclax maintenance, achieving sCR with the duration remission of 18.7 months. During induction, the patient experienced grade 3 neutropenia and infection. Conclusions:The combination therapy containing venetoclax is safe and manageable in MM patients with t(11; 14) and pPCL. The patients receiving early, regular, and adequate-dose treatment with venetoclax have better therapeutic efficacy.

Humans ; Waldenstrom Macroglobulinemia/genetics* ; East Asian People ; Chromosome Aberrations ; Lymphoma

Humans ; Prognosis ; Multiple Myeloma/diagnosis* ; Neoplasm Staging ; Hematopoietic Stem Cell Transplantation ; Patients ; Retrospective Studies

B-cell lymphoma is a group of heterogeneous hematologic malignant tumors originating from B cells, and it could be divided into invasive B-cell lymphoma and inert B-cell lymphoma. Currently, although disease remission rate has reached a high level, some patients still develop disease relapse or progression, thus, it is important to regularly monitor the disease and early identify the recurrence. At present, the recurrence of lymphoma mainly depends on imaging and clinical evaluation. However, some studies have shown that the minimal residual disease (MRD) monitoring based on flow or second-generation sequencing can provide a more accurate assessment of the depth of remission, predict the disease prognosis, and identify the early disease recurrence. This review summarizes the application of MRD in indolent lymphoma and aggressive lymphoma, mainly including the detection methods of MRD, research status and the application prospect of MRD in different lymphomas.