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Extramedullary solitary plasmacytoma (SP) is an uncommon tumor and is even rare in the head and neck locations. Here, we report the case of an 82-year-old man admitted to our department for the management of nasal cavity SP. Radiological investigation showed a locally advanced tumor making the patient a non-candidate for surgery. The patient had undergone radiotherapy alone to a total dose of 50 Gy, with 2 Gy per fraction five days a week. After a follow-up of nine months, the tumor recurred, and the patient was managed in the internal medicine department. He received palliative chemotherapy with the cyclophosphamide, dexamethasone, and thalidomide protocol which resulted in a good response. This case illustrates the diagnostic challenges and treatment complexities of SP, particularly in rare locations such as the nasal cavity.

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Amino acid metabolic remodeling is a hallmark of cancer, driving an increased nutritional demand for amino acids. Amino acids are pivotal for energetic regulation, biosynthetic support, and homeostatic maintenance to stimulate cancer progression. However, the role of phenylalanine in multiple myeloma (MM) remains unknown. Here, we demonstrate that phenylalanine levels in MM patients are decreased in plasma but elevated in bone marrow (BM) cells. After the treatment, phenylalanine levels increase in plasma and decrease in BM. This suggests that changes in phenylalanine have diagnostic value and that phenylalanine in the BM microenvironment is an essential source of nutrients for MM progression. The requirement for phenylalanine by MM cells exhibits a similar pattern. Inhibiting phenylalanine utilization suppresses MM cell growth and provides a synergistic effect with Bortezomib (BTZ) treatment in vitro and murine models. Mechanistically, phenylalanine deprivation induces excessive endoplasmic reticulum stress and leads to MM cell apoptosis through the ATF3-CHOP-DR5 pathway. Interference with ATF3 significantly affects phenylalanine deprivation therapy. In conclusion, we have identified phenylalanine metabolism as a characteristic feature of MM metabolic remodeling. Phenylalanine is necessary for MM proliferation, and its aberrant demand highlights the importance of low-phenylalanine diets as an adjuvant treatment for MM.

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We investigated immune cytopenia in multiple myeloma (MM) patients with concurrent acquired aplastic anemia (AA), focusing on three clinical cases treated with plasma cell-directed therapy. All three patients achieved partial response in MM and one patient experienced complete resolution of AA. Two patients had partial improvement in transfusion requirement but continued to suffer from severe AA, leading to immunosuppressive therapy (IST) with improvement of transfusion requirement in both patients. In vitro serum testing of these patients demonstrated platelet mitochondrial dysfunction and platelet apoptosis but did not show sera-specific inhibition of erythroid colony formation in progenitor cells. The levels of IL8 and IL15 were elevated in MM patients with AA, implicating their potential roles in this co-occurrence. Response to IST points to the possibility of myeloma-dysregulated immune system leading to autoreactive T-cell destruction of hematopoietic stem and progenitor cells, offering insights for developing new treatment for cytopenia in MM.

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OBJECTIVE: Talquetamab is the first GPRC5D-targeting bispecific antibody approved for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). This matching-adjusted indirect comparison (MAIC) study was conducted to compare the effectiveness of talquetamab vs selinexor-dexamethasone (sel-dex) and vs belantamab mafodotin (belamaf) in patients with TCE RRMM. METHODS: An unanchored MAIC was performed using individual patient-level data from patients treated with subcutaneous talquetamab 0.4 mg/kg weekly (QW) and 0.8 mg/kg every other week (Q2W) from MonumenTAL-1 (NCT03399799/NCT04636552) and published summary data for sel-dex from STORM (NCT02336815) and belamaf from DREAMM-2 (NCT0325678). Patients from MonumenTAL-1 who met key eligibility criteria for STORM and DREAMM-2 were included. Outcomes of interest were overall response rate (ORR), complete response or better (≥CR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: After adjustment for cross-trial differences, patients treated with both dosing schedules of talquetamab showed significantly better ORR, ≥CR, and DOR vs sel-dex and significantly higher ORR and ≥ CR vs belamaf; DOR was relatively similar to belamaf. PFS was significantly improved with talquetamab Q2W and numerically in favor of talquetamab QW vs sel-dex and significantly improved with both dosing schedules of talquetamab vs belamaf. OS was significantly improved with both dosing schedules of talquetamab vs sel-dex and was numerically in favor of both dosing schedules of talquetamab vs belamaf. CONCLUSION: These analyses show superior effectiveness of both talquetamab dosing schedules vs sel-dex and vs belamaf for most outcomes and highlight talquetamab as an effective treatment option for patients with TCE RRMM.

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Tumour microenvironment harbours diverse stress factors that affect the progression of multiple myeloma (MM), and the survival of MM cells heavily relies on crucial stress pathways. However, the impact of cellular stress on clinical prognosis of MM patients remains largely unknown. This study aimed to provide a cell stress-related model for survival and treatment prediction in MM. We incorporated five cell stress patterns including heat, oxidative, hypoxic, genotoxic, and endoplasmic reticulum stresses, to develop a comprehensive cellular stress index (CSI). Then we systematically analysed the effects of CSI on survival outcomes, clinical characteristics, immune microenvironment, and treatment sensitivity in MM. Molecular subtypes were identified using consensus clustering analysis based on CSI gene profiles. Moreover, a prognostic nomogram incorporating CSI was constructed and validated to aid in personalised risk stratification. After screening from five stress models, a CSI signature containing nine genes was established by Cox regression analyses and validated in three independent datasets. High CSI was significantly correlated with cell division pathways and poor clinical prognosis. Two distinct MM subtypes were identified through unsupervised clustering, showing significant differences in prognostic outcomes. The nomogram that combined CSI with clinical features exhibited good predictive performances in both training and validation cohorts. Meanwhile, CSI was closely associated with immune cell infiltration level and immune checkpoint gene expression. Therapeutically, patients with high CSI were more sensitive to bortezomib and antimitotic agents, while their response to immunotherapy was less favourable. Furthermore, in vitro experiments using cell lines and clinical samples verified the expression and function of key genes from CSI. The CSI signature could be a clinically applicable indicator of disease evaluation, demonstrating potential in predicting prognosis and guiding therapy for patients with MM.

Asunto(s)

Mieloma Múltiple , Nomogramas , Microambiente Tumoral , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Humanos , Pronóstico , Regulación Neoplásica de la Expresión Génica , Estrés Fisiológico , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Estrés del Retículo Endoplásmico , Resultado del Tratamiento , Femenino , Análisis por Conglomerados

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INTRODUCTION: In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved. AREAS COVERED: CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial. EXPERT OPINION: We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to the disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells furtherly.

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PURPOSE: Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells (PC) in the bone marrow (BM). B-cell maturation antigen (BCMA) is predominantly expressed in malignant plasma cells, and associated with the proliferation, survival, and progression of various myeloma cells. Given these important roles, BCMA emerges as an ideal target antigen for MM therapy. However, effective stratification of patients who may benefit from targeted BCMA therapy and real-time monitoring the therapeutic efficacy poses significant clinical challenge. This study aims to develop a BCMA targeted diagnostic modality, and preliminarily explore its potential value in the radio-immunotherapy of MM. EXPERIMENTAL DESIGN: Using zirconium-89 (89Zr, t1/2 = 78.4 h) for labeling the BCMA-specific antibody, the BCMA-targeting PET tracer [89Zr]Zr-DFO-BCMAh230430 was prepared. The EC50 values of BCMAh230430 and DFO-BCMAh230430 were determined by ELISA assay. BCMA expression was assessed in four different tumor cell lines (MM.1S, RPMI 8226, BxPC-3, and KYSE520) through Western blot and flow cytometry. In vitro binding affinity was determined by cell uptake studies of [89Zr]Zr-DFO-BCMAh230430 in these tumor cell lines. For in vivo evaluation, PET imaging and ex vivo biodistribution studies were conducted in tumor-bearing mice to evaluate imaging performance and systemic distribution of [89Zr]Zr-DFO-BCMAh230430. Immunochemistry analysis was performed to detect BCMA expression in tumor tissues, confirming the specificity of our probe. Furthermore, we explored the anti-tumor efficacy of Lutetium-177 labeled BCMA antibody, [177Lu]Lu-DTPA-BCMAh230430, in tumor bearing-mice to validate its radioimmunotherapy potential. RESULTS: The radiolabeling of [89Zr]Zr-DFO-BCMAh230430 and [177Lu]Lu-DTPA-BCMAh230430 showed satisfactory radiocharacteristics, with a radiochemical purity exceeding 99%. ELISA assay results revealed closely aligned EC50 values for BCMAh230430 and DFO-BCMAh230430, which are 57 pM and 67 pM, respectively. Western blot and flow cytometry analyses confirmed the highest BCMA expression level. Cell uptake data indicated that MM.1S cells had a total cellular uptake (the sum of internalization and surface binding) of 38.3% ± 1.53% for [89Zr]Zr-DFO-BCMAh230430 at 12 h. PET imaging of [89Zr]Zr-DFO-BCMAh230430 displayed radioactive uptake of 7.71 ± 0.67%ID/g in MM.1S tumors and 4.13 ± 1.21%ID/g in KYSE520 tumors at 168 h post-injection (n = 4) (P < 0.05), consistent with ex vivo biodistribution studies. Immunohistochemical analysis of tumor tissues confirmed higher BCMA expression in MM.1S tumors xenograft compared to KYSE520 tumors. Notably, [177Lu]Lu-DTPA-BCMAh230430 showed some anti-tumor efficacy, evidenced by slowed tumor growth. Furthermore, no significant difference in body weight was observed in MM.1S tumor-bearing mice over 14 days of administration with or without [177Lu]Lu-DTPA-BCMAh230430. CONCLUSIONS: Our study has successfully validated the essential role of [89Zr]Zr-DFO-BCMAh230430 in non-invasively monitoring BCMA status in MM tumors, showing favorable tumor uptake and specific binding affinity to MM tumors. Furthermore, our research revealed, as a proof-of-concept, the effectiveness of [177Lu]Lu-DTPA-BCMAh230430 in radioimmunotherapy for MM tumors. In conclusion, we present a novel BCMA antibody-based radiotheranostic modality that holds promise for achieving efficient and precise MM diagnostic and therapy.

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The present study aimed to evaluate the epidemiological, diagnostic and therapeutic data of hematological malignancies in pregnancy. Leukemia in pregnancy is rare, and literature data are not extensive. Risk factors, epidemiology and pathogenesis of these diseases are not fully developed. Furthermore, there is a detailed report on the complications in pregnancy and the overall (per trimester) management of these diseases, specifically their treatment strategy. The possibility of achieving a future pregnancy in women with leukemia is described in the present study. The limited clinical research data currently available is mainly due to the inability to conduct randomized clinical trials for ethical reasons. Further research is needed, firstly due to the importance of these diseases for the pregnant woman and the fetus, and secondly, due to the continuous development of novel anticancer drugs that aim to improve the prognosis of these diseases.

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In multiple myeloma (MM), while frequent mutations in driver genes are crucial for disease progression, they traditionally offer limited insights into patient prognosis. This study aims to enhance prognostic understanding in MM by analyzing pathway dysregulations in key cancer driver genes, thereby identifying actionable gene signatures. We conducted a detailed quantification of mutations and pathway dysregulations in 10 frequently mutated cancer driver genes in MM to characterize their comprehensive mutational impacts on the whole transcriptome. This was followed by a systematic survival analysis to identify significant gene signatures with enhanced prognostic value. Our systematic analysis highlighted 2 significant signatures, TP53 and LRP1B, which notably outperformed mere mutation status in prognostic predictions. These gene signatures remained prognostically valuable even when accounting for clinical factors, including cytogenetic abnormalities, the International Staging System (ISS), and its revised version (R-ISS). The LRP1B signature effectively distinguished high-risk patients within low/intermediate-risk categories and correlated with significant changes in the tumor immune microenvironment. Additionally, the LRP1B signature showed a strong association with proteasome inhibitor pathways, notably predicting patient responses to bortezomib and the progression from monoclonal gammopathy of unknown significance to MM. Through a rigorous analysis, this study underscores the potential of specific gene signatures in revolutionizing the prognostic landscape of MM, providing novel clinical insights that could influence future translational oncology research.

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Multiple myeloma (MM) is a malignancy of plasma cells accompanied by immune dysfunction. This study aimed to provide a comprehensive and dynamic characterization of the peripheral immune environment in MM patients and find its diagnostic and prognostic values for therapy. The peripheral immune profiles of MM inpatients and healthy controls were assessed by flow cytometry. A longitudinal study of immune subsets was observed during cycles of chemotherapy. The diagnostic and prognostic models were established based on immune subsets by the absolute shrinkage and selection operator (LASSO) and multivariate regression. MM patients possessed an impeded immune landscape, including reduced activation of B cells, increased effective T cells and regulatory T cells (Tregs), augmented CD16 expression on monocytes and dendritic cell percentages, decreased CD56dimCD16+ natural killer cells (NKs), and amplified CD56bright and HLA-DR+ natural killer T cells (NKTs). Chemotherapy has different dynamic effects on specific cells, of which 2 cycles is the key turning point. NKT, dendritic cells, naïve Tc and Th cells, HLA-DR+ Tc cells, CD56dim NKTs, CD16++ monocytes, and CD25+ B cells could have the diagnostic value, and a prognostic model including neutrophils, naïve Tc cells, CD56brightCD16dim NKs, and CD16+ dendritic cells was established with acceptable accuracy. Our data showed dynamic and abnormal peripheral immune profiles in MM patients, which had prognostic values and could provide the basis for clinical therapy.

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INTRODUCTION: Several frailty assessment tools exist for classifying older adults with multiple myeloma (MM) by their frailty status, such as the International Myeloma Working Group (IMWG) frailty score and the simplified frailty scale. The level of agreement between the IMWG frailty score and the simplified frailty scale remains unknown. MATERIALS AND METHODS: In a cross-sectional analysis of a prospective cohort study, we identified adults ≥50y initiating a new treatment regimen for MM who underwent a baseline geriatric assessment (GA). Using data from the GA and electronic health records, we measured IMWG frailty score and the simplified frailty scale, and classified patients by frailty status. We merged the fit and intermediate-fit categories of IMWG frailty score to create a binary category (frail, non-frail) for comparison with simplified frailty scale and measured their agreement using Cohen's Kappa statistic. We tested the diagnostic utility of simplified frailty scale as a screening tool using IMWG frailty score as the gold standard, using sensitivity, specificity, and decision curve analysis (DCA). RESULTS: Three hundred older adults were included with a median age at diagnosis of 64y; 56 % were male and 63 % were non-Hispanic White. By IMWG frailty score, 41 % were fit, 38 % intermediate-fit, and 21 % frail, while simplified frailty scale indicated 22 % frail and 78 % non-frail patients. The agreement between IMWG frailty score and simplified frailty scale was moderate (κ = 0.43); 19 % of the patients were misclassified. Despite discordance, when testing simplified frailty scale as a screening tool, we found a sensitivity of 56 % and specificity of 87 % to diagnose frailty. Substituting patient-reported performance status (PS) instead of physician reported ECOG PS led to a sensitivity of 91 % and specificity of 61 %. DCA showed that using simplified frailty scale (with patient reported PS) as a screening tool led to a 43-44 % reduction in the number of unnecessary GAs across reasonable threshold probabilities. DISCUSSION: IMWG frailty score and simplified frailty scale have limited agreement with each other. This creates a possibility of misclassification bias and poses difficulty in comparing existing literature on frail patients with MM. Despite discordance, simplified frailty scale may have a potential role as a screening tool, when using patient-reported PS.

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This Good Practice Paper provides recommendations for the use of advanced imaging for earlier diagnosis and morbidity prevention in multiple myeloma. It describes how advanced imaging contributes to optimal healthcare resource utilisation by in newly diagnosed and relapsed myeloma, and provides a perspective on future directions of myeloma imaging, including machine learning assisted reporting.

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BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Asunto(s)

Anticuerpos Monoclonales , Mieloma Múltiple , Insuficiencia Renal , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Humanos , Anticuerpos Monoclonales/uso terapéutico , Insuficiencia Renal/etiología , Insuficiencia Renal/tratamiento farmacológico , Resultado del Tratamiento

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The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Asunto(s)

Plaquetas , Inmunoterapia Adoptiva , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Receptores Quiméricos de Antígenos , Síndrome de Liberación de Citoquinas/terapia , Pruebas de Función Plaquetaria

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Introduction: Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM). In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated improved efficacy vs. standard of care (SOC; daratumumab plus pomalidomide and dexamethasone [DPd] or pomalidomide plus bortezomib and dexamethasone [PVd]) with a ≥ complete response (≥CR) rate of 73.1% vs. 21.8%. Methods: A cost-per-responder model was developed to assess the value of cilta-cel and SOC (87% DPd and 13% PVd) based on the CARTITUDE-4 trial data from a US mixed payer perspective (76.7% commercial, 23.3% Medicare). The model was developed using progression-free survival (PFS), overall survival (OS), and ≥CR endpoints from CARTITUDE-4 over a period of 25.4 months. Inpatient stays, outpatient visits, drug acquisition, administration, and monitoring costs were included. The base-case model assumed an inpatient setting for each cilta-cel infusion; another scenario included 30% outpatient and 70% inpatient infusions. Costs of managing grade 3-4 adverse events (AEs) and grade 1-4 cytokine release syndrome and neurotoxicity were included. Subsequent therapy costs were incurred after disease progression; terminal care costs were considered upon death events. Outcomes included total cost per treated patient, total cost per complete responder, and cost per month in PFS between cilta-cel and SOC. Costs were adjusted to 2024 US dollars. Results: Total cost per treated patient, total cost per complete responder, and total cost per month in PFS were estimated at $704,641, $963,941, and $30,978 for cilta-cel, respectively, and $840,730, $3,856,559, and $42,520 for SOC over the 25.4-month period. Cost drivers included treatment acquisition costs before progression and subsequent treatment costs ($451,318 and $111,637 for cilta-cel; $529,795 and $265,167 for SOC). A scenario analysis in which 30% of patients received an outpatient infusion (assuming the same payer mix) showed a lower cost per complete responder for cilta-cel ($956,523) than those with an infusion in the inpatient setting exclusively. Discussion: This analysis estimated that cost per treated patient, cost per complete responder, and cost per month in PFS for cilta-cel were remarkably lower than for DPd or PVd, highlighting the substantial clinical and economic benefit of cilta-cel for patients with RRMM.

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Análisis Costo-Beneficio , Inmunoterapia Adoptiva , Lenalidomida , Mieloma Múltiple , Talidomida , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/mortalidad , Mieloma Múltiple/tratamiento farmacológico , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Inmunoterapia Adoptiva/economía , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Talidomida/economía , Talidomida/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Receptores Quiméricos de Antígenos/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Masculino , Femenino , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Persona de Mediana Edad , Supervivencia sin Progresión , Resultado del Tratamiento , Anciano , Resistencia a Antineoplásicos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/economía

RESUMEN

Bortezomib, lenalidomide, and dexamethasone (VRD), and bortezomib, doxorubicin, and dexamethasone (PAD), are commonly used in induction regimens for patients with newly diagnosed multiple myeloma (NDMM) in China. This real-world study enrolled 390 patients, 195 receiving VRD and 195 receiving PAD induction. The primary endpoint was progression-free survival (PFS) and stringent complete remission/complete remission. Across the entire cohort, VRD demonstrated significantly improved five-year overall survival (OS) (74% vs. 59%, p = 0.0024) and five-year PFS (67% vs. 37%, p = 0.0018) compared to PAD. Notably, the median OS and PFS were not reached for VRD-treated patients, while they were 77 months (60-not reached [NR]) and 46 months (36-NR), respectively, for PAD. In patients with standard-risk cytogenetics, VRD showed superior five-year OS (83% vs. 58%, p = 0.0038) and PFS (78% vs. 48%, p = 0.0091) compared to PAD. However, these differences were not statistically significant in high-risk patients. For transplanted patients, VRD was associated with superior five-year OS (91% vs. 67%, p = 0.014) and PFS (79% vs. 47%, p = 0.015) compared to PAD. In non-transplanted patients, VRD showed a trend towards improved five-year OS (p = 0.085) and PFS (p = 0.073) compared to the PAD group. In conclusion, VRD displayed superior OS and PFS outcomes in standard-risk patients and those who underwent transplantation. These findings suggest potential advantages of VRD over PAD in real-world clinical settings for NDMM treatment. However, due to the imbalance in transplantation rates between the VRD and PAD groups, limitations in testing for high-risk cytogenetic abnormalities (HRA), and the difference between the received cycles and salvage therapies, the conclusions of this study should be interpreted with caution.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Doxorrubicina , Lenalidomida , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Masculino , Anciano , Adulto , Estudios Retrospectivos , Supervivencia sin Progresión , Anciano de 80 o más Años

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An 83-year-old female patient presented to our nephrology outpatient clinic with complaints of weakness, edema, abdominal pain, and constipation, with a preliminary diagnosis of chronic kidney failure related to heart failure. The patient had undergone mitral valve replacement surgery 10 years prior and was diagnosed with chronic renal failure six years prior. Laboratory tests revealed mild normochromic normocytic anemia, consistently high erythrocyte sedimentation rate (ESR) above 100 mm/h, and nephrotic-range proteinuria, prompting suspicion of multiple myeloma. Further investigations, including bone marrow aspiration, confirmed the diagnosis of multiple myeloma. During follow-up, the patient began to complain of difficulty swallowing and symptoms of microstomia. Upon further questioning, it was discovered that these symptoms had been present for more than 10 years. Immunoblot tests revealed positive centromere protein B (CENP-B), suggesting a diagnosis of scleroderma. Subsequently, during follow-up, bullous lesions appeared on the patient's chest. Biopsy samples confirmed a diagnosis of bullous pemphigoid (BP). The co-occurrence of scleroderma, multiple myeloma, and superimposed BP represents a rare and noteworthy case for publication.

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Background: Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication. Methods: Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software. Results: Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P < 0.001) compared to placebo group, Serious adverse events (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01), Rash (OR: 2.23; 95 % Cl: 1.62, 3.05; P < 0.001) and Vomiting (OR: 5.12; 95 % Cl: 3.36, 7.80; P < 0.001). The Serious adverse events of the treatment group were remarkably greater compared with the untreated group (OR: 1.60; 95 % Cl: 1.19, 2.14; P < 0.01). Conclusion: The study results proposed that proteasome inhibitors are effective in the multiple myeloma maintenance treatment compared with the placebo group. Bortezomib has certain advantages in prolonging PFS, followed by ixazomib and carfilzomib in terms of efficacy. Bortezombib may be superior to carfilzombib in extending OS. However, the adverse reactions caused by proteasome inhibitors, such as Peripheral neuropathy, Serious adverse events, Rash, Vomiting, etc., should be paid enough attention.

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BACKGROUND: Chromosome 1q21 aberrations are one of the most common cytogenetic abnormalities in patients with multiple myeloma (MM). However, the prognostic value remains controversial. This study aimed to determine the prognostic value of numerical abnormalities of chromosome 1q21 for newly diagnosed patients with MM patients in Chinese population. METHODS: We retrospectively analyzed 629 patients with newly diagnosed MM who received the detection of chromosome 1q21 by fluorescence in situ hybridization in China. RESULTS: Among 629 patients, 309 (49.1%) had 1q21 abnormalities, of which 187 (29.7%) had three copies and 122 (19.4%) had four or more copies. Patients with two copies of 1q21 had a significantly longer median overall survival (OS) than those with three copies or ≥4 copies and also had longer progression-free survival (PFS). However, patients with three or ≥4 copies had similar OS and PFS. Univariate Cox proportional hazards regression analyses determined that 1q21 aberrations are associated with shorter OS and PFS. 1q21 aberrations are also independent poor prognostic factors for OS and PFS in multivariable analyses. Del(17p), t(4;14), and t(14;16) are common high-risk cytogenetic abnormalities (HRCAs) in patients with MM. Patients with 1q21+ alone or 1q21+ combined with HRCAs had shorter OS and PFS than patients without cytogenetic abnormalities. Patients with 1q21+ and t(11;14) also had shorter PFS but had similar OS than patients without cytogenetic abnormalities. CONCLUSION: Our study showed that chromosome 1q21 aberrations are poor prognostic factors for newly diagnosed patients with MM.