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World Journal of Surgical Oncology Jun 2024To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a...
BACKGROUND
To investigate the prognosis of patients with Multiple Myeloma (MM) after surgery, analyze the risk factors leading to adverse postoperative outcomes, and establish a nomogram.
METHODS
Clinical data from 154 patients with MM who underwent surgery at our institution between 2007 and 2019 were retrospectively analyzed. Assessing and comparing patients' pain levels, quality of life, and functional status before and after surgery (P < 0.05) were considered statistically significant. The Kaplan-Meier survival curve was used to estimate the median survival time. Adverse postoperative outcomes were defined as worsened symptoms, lesion recurrence, complication grade ≥ 2, or a postoperative survival period < 1 year. Logistic regression analysis was used to determine the prognostic factors. Based on the logistic regression results, a nomogram predictive model was developed and calibrated.
RESULTS
Postoperative pain was significantly alleviated in patients with MM, and there were significant improvements in the quality of life and functional status (P < 0.05). The median postoperative survival was 41 months. Forty-nine patients (31.8%) experienced adverse postoperative outcomes. Multivariate logistic regression analysis identified patient age, duration of MM, International Staging System, preoperative Karnofsky Performance Status, and Hb < 90 g/L as independent factors influencing patient prognosis. Based on these results, a nomogram was constructed, with a C-index of 0.812. The calibration curve demonstrated similarity between the predicted and actual survival curves. Decision curve analysis favored the predictive value of the model at high-risk thresholds from 10% to-69%.
CONCLUSION
This study developed a nomogram risk prediction model to assist in providing quantifiable assessment indicators for preoperative evaluation of surgical risk.
Topics: Humans; Nomograms; Multiple Myeloma; Male; Female; Middle Aged; Retrospective Studies; Prognosis; Aged; Quality of Life; Survival Rate; Follow-Up Studies; Postoperative Complications; Adult; Risk Factors; Aged, 80 and over; Pain, Postoperative
PubMed: 38918829
DOI: 10.1186/s12957-024-03453-y -
Clinical and Experimental Medicine Jun 2024Dysregulated lipid metabolism in the bone marrow microenvironment (BMM) plays a vital role in multiple myeloma (MM) development, progression, and drug resistance....
Dysregulated lipid metabolism in the bone marrow microenvironment (BMM) plays a vital role in multiple myeloma (MM) development, progression, and drug resistance. However, the exact mechanism by which lipid metabolism impacts the BMM, promotes tumorigenesis, and triggers drug resistance remains to be fully elucidated.By analyzing the bulk sequencing and single-cell sequencing data of MM patients, we identified lipid metabolism-related genes differential expression significantly associated with MM prognosis, referred to as LMRPgenes. Using a cohort of ten machine learning algorithms and 117 combinations, LMRPgenes predictive models were constructed. Further exploration of the effects of the model risk score (RS) on the survival status, immune status of patients with BMM, and response to immunotherapy was conducted. The study also facilitated the identification of personalized therapeutic strategies targeting specified risk categories within patient cohorts.Analysis of the scRNA-seq data revealed increased lipid metabolism-related gene enrichment scores (LMESs) in erythroblasts and progenitor, malignant, and Tprolif cells but decreased LMESs in lymphocytes. LMESs were also strongly correlated with most of the 50 hallmark pathways within these cell populations. An elevated malignant cell ratio and reduced lymphocytes were observed in the high LMES group. Moreover, the LMRPgenes predictive model, consisting of 14 genes, showed great predictive power. The risk score emerged as an independent indicator of poor outcomes. Inverse relationships between the RS and immune status were noted, and a high RS was associated with impaired immunotherapy responses. Drug sensitivity assays indicated the effectiveness of bortezomib, buparlisib, dinaciclib, staurosporine, rapamycin, and MST-312 in the high-RS group, suggesting their potential for treating patients with high-RS values and poor response to immunotherapy. Ultimately, upon verification via qRT-PCR, we observed a significant upregulation of ACBD6 in NDMM group compared to the control group.Our research enhances the knowledge base regarding the association between lipid metabolism-related genes (LMRGs) and the BMM in MM patients, offering substantive insights into the mechanistic effects of the BMM mediated by LMRGs.
Topics: Humans; Lipid Metabolism; Tumor Microenvironment; Multiple Myeloma; Bone Marrow; Transcriptome; Gene Expression Profiling; Prognosis; Gene Expression Regulation, Neoplastic
PubMed: 38916672
DOI: 10.1007/s10238-024-01398-w -
Frontiers in Immunology 2024Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to...
INTRODUCTION
Chimeric antigen receptor (CAR) T-cell therapy (CAR T therapy) is a treatment option for patients with relapsed or refractory multiple myeloma that has led to unprecedented treatment outcomes. Among CAR T therapies available, ciltacabtagene autoleucel (cilta-cel) is a good candidate for outpatient administration due to its generally predictable safety profile. There are multiple advantages of outpatient administration of cilta-cel, including reduced healthcare burden, expanded access, and patient autonomy. This mixed methods qualitative study aimed to identify key factors for outpatient administration of CAR T and best practice recommendations by combining a targeted literature review with expert interviews and panels.
METHODS
The targeted review (Phase 1) aimed to identify factors for outpatient CAR T administration in the US and determine key topics for the exploratory interviews (Phase 2) and expert panels (Phase 3), which aimed to inform on best practices and challenges of outpatient CAR T administration (focusing on cilta-cel). Participants in clinical and administrative positions based in treatment centers that had experience with real-world outpatient administration of cilta-cel were recruited.
RESULTS
Seventeen studies were identified in Phase 1. Key factors for outpatient administration included the development of protocols for CAR T complications, education for caregivers, outpatient specialists, hospital staff, and emergency services staff for identification and referral after possible adverse events, the creation of multidisciplinary teams for effective communication and management, straightforward patient intake processes encompassing financial eligibility review and provision of patient education materials, and close patient monitoring throughout the treatment journey. In Phase 2, 5 participants from 2 centers were interviewed. In Phase 3, 14 participants across 6 treatment centers were interviewed. Two 90-minute virtual panel discussions took place. All participants agreed that cilta-cel can be safely and effectively administered in an outpatient setting. Key recommendations included the creation of educational resources for patients and caregivers, the development of standard operating procedures, dedicated outpatient infrastructure and establishment of interdisciplinary teams, outpatient monitoring for toxicity management, and monitoring of the reimbursement landscape.
DISCUSSION
This study offers a comprehensive understanding of the feasibility of outpatient cilta-cel administration in participating CAR T centers and provides actionable recommendations while acknowledging existing challenges.
Topics: Humans; Multiple Myeloma; Immunotherapy, Adoptive; Outpatients; Biological Products; Ambulatory Care; Receptors, Chimeric Antigen; Male
PubMed: 38915401
DOI: 10.3389/fimmu.2024.1405452 -
Journal of Hematology & Oncology Jun 2024It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of...
It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.
Topics: Humans; Multiple Myeloma; Aged; Prospective Studies; Male; Female; Aged, 80 and over; Dexamethasone; Antineoplastic Combined Chemotherapy Protocols; Frailty; Lenalidomide; Bortezomib; Precision Medicine; Frail Elderly; Geriatric Assessment; Antibodies, Monoclonal
PubMed: 38915117
DOI: 10.1186/s13045-024-01569-y -
Archives of Public Health = Archives... Jun 2024Oncological home hospitalization (HH) was implemented in a Belgian context to evaluate the feasibility of oncological HH. In a first HH model (HH1), implemented by three...
BACKGROUND
Oncological home hospitalization (HH) was implemented in a Belgian context to evaluate the feasibility of oncological HH. In a first HH model (HH1), implemented by three Belgian hospitals, two home nursing organizations and a grouping of independent nurses, the blood draw and monitoring prior to intravenous therapy was performed by a trained home nurse at the patient's home the day before the visit to the day hospital. In a second HH model (HH2), implemented in one hospital, the administration of two subcutaneous treatments (Azacitidine and Bortezomib) for myelodysplastic syndrome and multiple myeloma were provided at home instead of in the hospital. A previous study on this pilot showed that oncological HH is feasible and safe and improves the Quality of Life. The aim of this study is to investigate the cost and reimbursement of cancer treatment in these two HH models compared to the Standard of Care (SOC).
METHODS
A bottom-up micro-costing study was conducted to compare the costs and revenues for the providers (hospitals and home care organizations) of the SOC and the HH models.
RESULTS
Costs associated to HH were higher than the SOC in the hospital. Comparing revenues with costs, the research revealed that the reimbursement from the National Health Insurance of HH for oncological patients is insufficient. In HH1, costs were higher than in the SOC (+ €50.4). There was a reduction in costs in the hospital by moving the blood draw to the home setting (-€23.9), but the costs in home care were higher (+ €74.3). The extra revenues in home care (+ €33.6) were insufficient to cover the costs. The cost difference between the SOC and HH2 (+ €9.5 for Azacetidine) was smaller than in HH1. But, there was almost no funding for subcutaneous administration in home care. If the product is administered in a day hospital, the hospital receives a revenue of €124 per administration, while in home care the funding is €5 per visit.
CONCLUSION
Costs of HH are higher and the reimbursement from Belgian NHI is insufficient to organize HH. As a result, HH for oncology patient is still limited in Belgium.
PubMed: 38915071
DOI: 10.1186/s13690-024-01317-1 -
Scientific Reports Jun 2024Multiple myeloma (MM) is a plasma cell disorder accounting for approximately 10% of hematologic malignancies. There is limited epidemiological evidence regarding the...
Multiple myeloma (MM) is a plasma cell disorder accounting for approximately 10% of hematologic malignancies. There is limited epidemiological evidence regarding the long-term trends and disparities in MM in the US. We conducted a multiple time point cross-sectional study using MM incidence rate data from the Surveillance, Epidemiology, and End Results (SEER) database and mortality data from the CDC Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) Underlying Cause of Death database between 1999 and 2020. During this period, MM incidence has steadily increased, while MM mortality has steadily decreased, with substantial racial and ethnic disparities. Non-Hispanic Black individuals exhibited the highest incidence rates, which consistently rose from 12.02 (95% CI 10.54, 13.64) in 1999 to 14.20 (95% CI 12.93, 15.55) per 100,000 population by 2020. Non-Hispanic American Indian/Native Alaskans and Asian/Pacific Islanders demonstrated the lowest incidence rates of 5.59 (95% CI 2.69, 10.04) and 3.56 (95% CI 2.94, 4.27) per 100,000 population in 1999 to 5.76 (95% CI 3.49, 8.90) and 3.92 (95% CI 3.46, 4.42) per 100,000 population, respectively, by 2020. Disparities by gender, age, US census region, and rurality were observed, underscoring the importance of targeted, equity-centered interventions and MM screening initiatives for at-risk populations.
Topics: Humans; Multiple Myeloma; United States; Male; Female; Incidence; Middle Aged; Aged; SEER Program; Adult; Cross-Sectional Studies; Aged, 80 and over; Ethnicity
PubMed: 38914692
DOI: 10.1038/s41598-024-65590-4 -
Clinical Chemistry and Laboratory... Jun 2024Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases...
OBJECTIVES
Monoclonal gammopathies frequently associate with hemostatic alterations. Thrombotic events occur with high incidence particularly upon treatment, while in rarer cases hemorrhagic diathesis can be observed. The pathology of these tendencies could be caused by thrombocytopenia or hyperviscosity burden of circulating monoclonal antibodies. Studies also suggest interference of monoclonal antibodies with primary hemostasis. We isolated monoclonal whole IgG paraproteins from two myeloma patients to observe their effect on thrombin formation and fibrin polymerization.
METHODS
Monoclonal whole IgG was prepared from sera of two newly diagnosed untreated multiple myeloma patients and control normal plasma samples. Fibrin formation was measured using thrombin time and dilute prothrombin time tests and thrombin formation was detected with a fluorimetric thrombin generation assay. In addition, molecular interactions were investigated by surface plasmon resonance (SPR).
RESULTS
Thrombin time was prolonged upon addition of monoclonal IgG even at 30 g/L by 12 %, increasing up to 36 % at 60 g/L concentration. Dilute prothrombin time was prolonged by 20 % even at 30 g/L. Thrombin generation assay indicated an impairment in thrombin formation at the presence of monoclonal IgG compared to polyclonal at equivalent concentration. By an SPR assay we determined that both clonality IgG preparations interacted with fibrinogen, however interaction with human thrombin was only detected with monoclonal immunoglobulins (K=1.03 × 10 M).
CONCLUSIONS
Here we provide evidence that isolated monoclonal whole IgG from myeloma patients can impair both fibrin and thrombin formation and we demonstrate by SPR assay that it interacts with components of the final phase of the coagulation system.
PubMed: 38912717
DOI: 10.1515/cclm-2024-0252 -
Frontiers in Oncology 2024Extramedullary plasmacytoma (EMP) is an uncommon solitary tumor originating from neoplastic plasma cells located outside the bone marrow. Despite its rarity, the...
INTRODUCTION
Extramedullary plasmacytoma (EMP) is an uncommon solitary tumor originating from neoplastic plasma cells located outside the bone marrow. Despite its rarity, the occurrence of EMP without a concurrent diagnosis of multiple myeloma (MM) is considered extremely rare. Approximately 80-90% of EMP cases are found in the head and neck region, with a higher incidence in men aged between 50 and 60 years. The current treatment modalities include radiotherapy (RT) as a first-line approach, with surgery or chemotherapy regarded as other therapeutic options. While RT proves effective in the majority of EMP cases, there are instances where the tumor remains refractory to radiation. In this case report, we present an unusual scenario of EMP resistant to RT without concurrent signs of multiple myeloma which was successfully treated with surgery followed by systemic therapy.
CASE REPORT
A 72-year-old male was admitted to the Head and Neck Cancer Clinic with a 6-month history of swallowing difficulties. He denied experiencing weight loss or pain on swallowing. Basic laboratory tests yielded results within normal limits, except for beta-2 microglobulin. Physical examination revealed an enlarged submandibular lymph node on the right side. Fiberoptic examination identified a soft tissue polypoid mass within the right piriform fossa, slightly protruding into the vocal slit. A CT scan displayed a well-circumscribed 2 cm polypoid, homogeneously enhancing soft tissue mass adjacent to the posterior surface of the epiglottis and the right side of the tongue base. Bone marrow biopsy revealed no abnormalities, and there were no clinical or laboratory signs of multiple myeloma. Based on the tumor biopsy results and imaging studies, a diagnosis of EMP was made. Due to the lack of response to RT, surgical removal of the tumor was pursued, followed by systemic therapy. Ultimately, the patient achieved full recovery with effective disease control.
CONCLUSION
In conclusion, EMP without concurrent multiple myeloma is an exceedingly rare condition that demands a multidisciplinary approach for both diagnosis and treatment. Moreover, although RT continues to be the primary standard treatment for EMP, in some cases other therapeutic regimens prove to be successful.
PubMed: 38912063
DOI: 10.3389/fonc.2024.1353943 -
JACC. Case Reports Jul 2024We introduce the innovative use of technetium-99m-labeled macroaggregated albumin to diagnose high-output heart failure in a patient with multiple myeloma with...
We introduce the innovative use of technetium-99m-labeled macroaggregated albumin to diagnose high-output heart failure in a patient with multiple myeloma with persistent congestion symptoms. Symptom resolution occurred with lenalidomide and steroids. This marks the first clinical use of technetium-99m-labeled macroaggregated albumin for clarifying high-output heart failure etiology.
PubMed: 38912004
DOI: 10.1016/j.jaccas.2024.102387 -
Frontiers in Immunology 2024Infections are common in plasma cell cancer multiple myeloma (MM) due to disease-related immune deficiencies and cancer treatment. Myeloma cells express Toll-like...
Toll-like receptor signaling in multiple myeloma cells promotes the expression of pro-survival genes B-cell lymphoma 2 and MYC and modulates the expression of B-cell maturation antigen.
Infections are common in plasma cell cancer multiple myeloma (MM) due to disease-related immune deficiencies and cancer treatment. Myeloma cells express Toll-like receptors (TLRs), and TLR activation has been shown to induce proliferative and pro-survival signals in cancer cells. MM is a complex and heterogeneous disease, and expression levels of TLRs as well as downstream signaling components are likely to differ between patients. Here, we show that in a large cohort of patients, TLR1, TLR4, TLR6, TLR9, and TLR10 are the most highly expressed in primary CD138 cells. Using an MM cell line expressing TLR4 and TLR9 as a model, we demonstrate that TLR4 and TLR9 activation promoted the expression of well-established pro-survival and oncogenes in MM such as , , , and . TLR4 and TLR9 activation inhibited the efficacy of proteasome inhibitors bortezomib and carfilzomib, drugs used in the treatment of MM. Inhibiting the autophagosome-lysosome protein degradation pathway by hydroxychloroquine (HCQ) diminished the protective effect of TLR activation on proteasome inhibitor-induced cytotoxicity. We also found that TLR signaling downregulated the expression of , the gene encoding for B-cell maturation antigen (BCMA). , , and were upregulated in approximately 50% of primary cells, while the response to TLR signaling in terms of expression was dichotomous, as an equal fraction of patients showed upregulation and downregulation of the gene. While proteasome inhibitors are part of first-line MM treatment, several of the new anti-MM immune therapeutic drugs target BCMA. Thus, TLR activation may render MM cells less responsive to commonly used anti-myeloma drugs.
Topics: Humans; Multiple Myeloma; Signal Transduction; B-Cell Maturation Antigen; Cell Line, Tumor; Toll-Like Receptors; Proto-Oncogene Proteins c-myc; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins c-bcl-2; Bortezomib; Male
PubMed: 38911853
DOI: 10.3389/fimmu.2024.1393906