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Background and objective Skeletal involvement in multiple myeloma frequently results in pathological fractures, which significantly increase morbidity and functional disability. Advanced imaging modalities such as PET/CT and whole-body MRI are considered reference techniques for disease assessment; however, their availability remains limited in many healthcare systems. The objective of this study is to evaluate the association between 99mTc-MIBI uptake and pathological fracture occurrence in the appendicular skeleton of patients with multiple myeloma and to determine whether radiotracer uptake and lesion morphology predict fracture timing. Methods A retrospective observational study was conducted, including patients with histologically confirmed multiple myeloma who underwent technetium-99m sestamibi (99mTc-MIBI) scintigraphy between 2014 and 2021. Radiotracer uptake was assessed qualitatively. Fractures were confirmed radiographically and classified as early (less than six months) or late (more than six months). Logistic regression analysis was performed to identify independent predictors. Results The cohort included 121 patients (median age 61.5 ± 12.5 years), including 69 men (57%) and 52 women (43%). Uptake of 99mTc-MIBI occurred most frequently in the humerus (31; 27.9%), axial skeleton (19; 17.1%), and femur (10; 9.0%). Pathological fractures occurred in 94 patients (77.7%), including 86 early fractures (71.1%) and eight late fractures (6.6%). In bivariate analysis, cortical erosion (χ² = 2.9; p = 0.023) and age >63 years (t = 2.4; p = 0.02) were associated with fracture. Multivariate logistic regression identified expansile lesions with cortical erosion as the strongest predictor of fracture (OR 2.1; 95% CI: 0.8-5.7). Conclusions 99mTc-MIBI scintigraphy may represent a valuable adjunct imaging modality for the assessment of skeletal involvement in patients with multiple myeloma, particularly in resource-limited settings where advanced imaging techniques such as whole-body MRI or PET/CT are not readily accessible. Although cortical erosion continues to be the most reliable structural predictor of impending fracture, 99mTc-MIBI uptake offers complementary functional insight into the metabolic activity and tumor burden of myelomatous lesions. This functional information may be especially relevant in identifying lesions at higher risk of progression or early structural compromise, even before overt radiographic changes become evident. Therefore, 99mTc-MIBI could potentially contribute to a more comprehensive risk assessment when integrated with conventional imaging findings and clinical parameters. However, given the heterogeneity of disease presentation and the limited sample size of current studies, including the present analysis, these findings should be interpreted with caution. Future prospective studies with larger cohorts and standardized imaging protocols are warranted to further elucidate the prognostic value of 99mTc-MIBI uptake and to determine its potential role in fracture risk stratification and treatment decision-making algorithms.

Proteins belonging to the Schlafen family are interferon-inducible and participate in the regulation of antiviral responses, immune signaling, and proteotoxic stress. SLFN11 kills cells with replicative damage, serving as a predictive biomarker for chemotherapeutic response. SLFN11 is epigenetically downregulated in ≈50% of solid tumors. Here we examined SLFN11 expression and significance in multiple myeloma (MM). Using TCGA and MMRF CoMMpass datasets, we find SLFN11 is consistently highly expressed across MM subtypes except CD1 and MAF/MAFB. CD138-positive normal and myeloma plasma cells retain SLFN11 expression even when proliferative activity (MKI67/Ki-67) increases with disease progression. SLFN11 expression strongly correlates with super-enhancer-driven plasma cell transcriptional programs. We report that bortezomib, a first-line MM treatment, induces SLFN11 accumulation in nucleoli with suppression of ribosomal RNA synthesis. SLFN11 knockout cells show enhanced bortezomib sensitivity and exatecan resistance, supporting SLFN11's protective role in proteotoxic stress and sensitizing role in replication stress. This study reveals that SLFN11 undergoes nucleolar translocation in response to proteasome inhibition in multiple myeloma, suppressing ribosomal RNA synthesis and conferring resistance to bortezomib while maintaining sensitivity to topoisomerase I inhibitors, thereby establishing SLFN11 as a dual-function biomarker for precision therapy selection in this disease.

Serum protein electrophoresis (SPE) is widely used to detect monoclonal gammopathies and other hematologic or inflammatory disorders. IgG monoclonal proteins typically migrate in the gamma region, while IgA frequently migrates in the beta region. However, IgG migration in the β2 region is an exceptionally rare occurrence that can pose significant diagnostic challenges. We present the case of a 76-year-old woman who was initially diagnosed with acute bilateral pulmonary embolism and deep vein thrombosis as the first clinical manifestation of multiple myeloma. Laboratory findings revealed hypercalcemia, mild anemia, and a monoclonal IgG lambda peak in the β2 region, which was confirmed by immunofixation. Echocardiography revealed left ventricular dilation with preserved right-sided heart structures. Ten days later, the patient developed cauda equina syndrome due to spinal involvement, requiring urgent surgical decompression. This case highlights three exceptionally rare and clinically significant features: (1) IgG monoclonal protein migration in the β2 region, (2) pulmonary embolism as the first manifestation of multiple myeloma, and (3) severe skeletal complications after minimal trauma. Clinicians should consider underlying monoclonal gammopathy in unexplained thromboembolic events and exercise caution when interpreting atypical SPE patterns, which may be crucial for early diagnosis. The unusual combination of these findings underscores the importance of a comprehensive approach to diagnosing plasma cell disorders. Recognition of more anodal IgG migration and awareness of thromboembolic presentation are crucial to ensure early diagnosis and appropriate management of multiple myeloma.

The immunological synapse, a highly organized cell-cell junction, is an important fulcrum for effective T-cell-mediated killing of cancer cells. In multiple myeloma, however, therapeutic resistance reflects multiple interacting layers, including synaptic disruption, clonal evolution, metabolic reprogramming, and spatially heterogeneous bone-marrow niches, all of which can contribute to T-cell dysfunction and immune escape. This review examines the immunological synapse as a potentially modifiable intercellular interface: we describe how the bone marrow niche impairs synaptic function and summarize strategies that may help restore synaptic structure and signaling. We explore how the myeloma niche deranges synaptic function and then detail innovative strategies to restore its fidelity. We analyze how BiTEs establish synaptic contacts and how CAR-T cells assemble modified synaptic interfaces that have distinct structural and signaling properties; we then compare shared and divergent mechanisms of action. Looking forward, we discuss next-generation approaches, including trispecific antibodies, armored/logic-gated CAR-Ts, niche-modifying agents, and synaptic nanotechnology, which aim to create specific, resilient, and context-aware cytolytic junctions. By framing therapeutic progress through the lens of synaptic engineering, this narrative review selectively integrates mechanistic, translational, and clinical reports supporting synapse-directed interventions, while explicitly separating preclinical models from early-phase and randomized clinical evidence so that hypothesis-generating findings are not treated as equivalent to patient outcome data.

Multiple myeloma is an incurable hematologic malignancy, although therapeutic advances have improved survival. BCMA-directed CAR-T cell therapy has shown high response rates in relapsed or refractory multiple myeloma (RRMM), but efficacy and toxicity vary across trials. A rigorous synthesis of current evidence is needed to better define these outcomes. We performed a systematic review and meta-analysis of prospective interventional trials published from inception to January 2026 evaluating BCMA-targeted CAR-T therapies in adults with RRMM. Trials reporting efficacy or safety outcomes were included. Pooled estimates with 95% confidence intervals (CI) were calculated in R. Heterogeneity was assessed using the I² statistic, publication bias with Egger's regression, and stability with leave-one-out sensitivity analysis. Fourteen clinical trials including 1,278 patients with RRMM and a median of 3 to 8 prior lines of therapy were included1-4. The pooled overall response rate (ORR) was 86% (95% CI: 80-90%; I² = 75.9%). Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3% of patients (95% CI: 2-4%; I² = 0%). Discontinuation due to toxicity occurred in 4% (95% CI: 1-9%; I² = 68.2%), and treatment-related mortality in 5% (95% CI: 3-9%; I² = 64%). Additional efficacy and safety outcomes, including disease control rate and grade ≥ 3 hematologic toxicities, were also assessed. BCMA-directed CAR-T cell therapy demonstrates high efficacy in RRMM with a low incidence of severe neurotoxicity. However, severe hematologic toxicities are frequent and treatment-related mortality remains clinically relevant, highlighting the need for optimized patient selection and toxicity mitigation.

Multiple myeloma outcomes vary widely, with risk stratification typically based on baseline characteristics. Functionally high-risk multiple myeloma (FHRMM), defined by early relapse within 12 months of initial therapy or autologous stem cell transplant, is associated with poor prognosis. However, the continued prognostic impact of baseline high-risk features within the FHRMM cohort remains unclear. This study analyzed 181 FHRMM patients from the CoMMpass dataset, categorized into standard-risk (SRG) and high-risk (HRG) groups based on baseline cytogenetics and ISS stage. Despite SRG patients possessing more favorable baseline risk profiles, including lower SKY92 scores, their overall survival (OS) was not significantly different from HRG patients (20.7 vs. 18.1 months, p = 0.059). Treatment regimens and response rates were comparable between groups. Within the FHRMM cohort, only baseline ISS stage I retained prognostic significance for OS. In conclusion, FHR status overrides traditional baseline risk factors in determining prognosis. Patients experiencing early relapse should be considered uniformly high-risk, highlighting the need for effective salvage therapies and consideration of novel treatments like CAR T-cell therapies.

We present real-world evidence of patient-physician communication for patients with newly diagnosed multiple myeloma (NDMM) who have not received hematopoietic stem cell transplantation. An observational survey study was conducted in Japan (September‒November 2024). Patients with NDMM completed a self-reported 34-item survey (online or paper-based), and hematologists treating patients with multiple myeloma completed a self-reported 18-item survey online. Communication status between patients and physicians and information on patients' treatment expectations, values, emotions, knowledge, and treatment decision-making preferences at both treatment initiation and disease stabilization were summarized. Overall, 220 patients and 120 physicians were included. At both treatment initiation and disease stabilization, 45.9% and 50.3% of patients, respectively, had treatment options presented or explained to them, and 23.6% and 25.2%, respectively, were asked about their preferences; conversely, 82.5% and 65.0% of physicians, respectively, presented or explained treatment options to patients, and 67.5% and 50.8%, respectively, asked patients about their preferences. Patients' emotions shifted from negative to positive, their knowledge of the disease and treatment increased, and their treatment expectations changed from treatment initiation to disease stabilization. Overall, 44.5% of patients preferred a shared role in decision-making; however, only 21.8% had a shared role in actual practice at treatment initiation. There was a discrepancy in perceptions of communication between patients and physicians. Patients' expectations, emotions, and knowledge changed from treatment initiation to disease stabilization. Physicians should understand these changes and communicate more effectively about treatment options and plans at both treatment initiation and disease stabilization. Trial Registration: University Hospital Medical Information Network Center: UMIN000055606.

Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy, has shown deep and durable responses in clinical trials for relapsed/refractory multiple myeloma (RRMM). This study aimed to provide a descriptive evaluation of outcomes among patients who received cilta-cel in clinical practice, including among subgroups based on patient characteristics that could impact outcomes. This retrospective study used Loopback Analytics electronic medical records (02/2021-06/2025) to identify adults with RRMM who received cilta-cel after ≥4 prior lines of therapy (LOT). The index date was defined as the cilta-cel infusion date. As a surrogate outcome for progression-free survival, treatment-free interval (TFI) was defined as the time from infusion to the earliest of initiation of next treatment or death. Overall survival (OS) was defined as the time from infusion to death. To more accurately identify patients with a next LOT, the date of next treatment was defined as the earliest fill or administration for an eligible agent ≥60 days post-infusion, provided that the patient had ≥2 fills or administrations of the same agent. Kaplan-Meier analyses assessed TFI and OS in all patients and by subgroups defined by age (≥75 years), frailty index score (mild-to-severe frailty) in the three months pre-infusion, and CRAB symptoms (hypercalcemia, renal impairment, anemia, or bone lesions; ≥1 symptom) in the one month pre-infusion. Among 203 patients, 8.4% were aged ≥75 years, 14.8% were mildly-to-severely frail, and 38.4% had ≥1 CRAB symptom. Median (interquartile range) follow-up was 17.6 (12.0-24.2) months. For TFI, the estimated Kaplan-Meier rates (95% confidence interval) at 12 and 18 months post-infusion were 85.5% (79.6%-89.8%) and 76.5% (69.0%-82.4%), respectively, while the OS rates were 95.1% (90.8%-97.4%) and 93.0% (87.8%-96.0%). Across subgroups, TFI remained generally consistent with the overall population and OS remained high. This study demonstrated favorable outcomes among patients with RRMM who received cilta-cel after ≥4 prior LOT in clinical practice, including among patients with older age, higher frailty index score, and recent presence of CRAB symptoms.

Minimal residual disease (MRD) has been endorsed by FDA Oncology Drugs Advisory Committee as an endpoint for accelerated approval in Multiple Myeloma (MM) based on individual patient data collected from randomized trials. However, emerging data from recent trials were not included. A novel AI-assisted framework is proposed, which automates information identification and extraction, providing up-to-date analyses that confirm moderate trial-level and strong individual-patient-level association between MRD-CR and survival endpoints in MM. Specifically, this study utilized an AI-assisted framework that identifies relevant studies and filters critical information to analyze published data via two independent objectives. Firstly, we examined the trial-level association by the coefficients of determination (R^2) and its 95% confidence intervals (CIs) based on published statistics of treatment effects on MRD and various endpoints. Next, we generated synthetic IPD with covariates through AI-curated tools to estimate the individual-level association. The AI tool searched for eligible randomized clinical trials. A total of 20 two-arm comparisons from 19 RCTs were analyzed. Trial-level analysis showed an R² of 0.71 (95% CI 0.52 - 0.89) pooling disease subpopulations. Furthermore, AI techniques were applied to create synthetic individual data, combining information extracted from Kaplan-Meier curves and subgroup analyses from published literatures. Using generated synthetic data, we estimated the individual-level correlation between MRD-CR rates and PFS outcomes with a bivariate copula model and calculated a Global OR of 7.28 (95% CI 5.60-8.95).

Severe cutaneous adverse reactions are a spectrum of life-threatening immune mediated adverse drug reactions characterized by extensive skin involvement with the potential for organ injury. It is composed of four main entities: drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. With prominent hypereosinophilia (>1500 eosinophils/µL), hypereosinophilic syndrome also warrants consideration, albeit rarely triggered by medications. In addition, there may also be concern for infectious etiologies, particularly in patients with notable travel history or immunosuppression. Herein, we present the case of a 65-year-old man with multiple myeloma who was started on several medications simultaneously for the induction of chemotherapy and who developed a full-body pruritic and maculopapular rash and peripheral eosinophilia 2-to-4 weeks after initiation of these medications. He had a recalcitrant course, which required multiple rounds of systemic steroids and other treatments. After a detailed history, physical examination, and additional investigation coupled with high clinical suspicion, a diagnosis, and treatment plan was made.

Background/Objectives: Serum protein electrophoresis (SPE) is a widely used laboratory test for the detection and monitoring of monoclonal gammopathies, including multiple myeloma (MM). Although SPE is usually recommended in the presence of specific clinical or laboratory abnormalities, monoclonal gammopathies may occasionally develop rapidly and without typical symptoms. This case report aims to emphasize the diagnostic value of SPE in identifying an unexpected and fast-evolving monoclonal gammopathy. Methods: We report the clinical and laboratory eight-month follow-up of a 58-year-old male who initially underwent SPE for unrelated clinical conditions. Serial SPE analyses were performed using capillary zone electrophoresis. When abnormalities emerged, immunotyping and serum free light chain (FLC) assays were conducted. The diagnostic workup was completed with bone marrow aspiration, flow cytometry, and imaging studies according to current international diagnostic criteria. Results: The initial SPE (November 2023) showed a normal protein profile. After eight months, follow-up SPE revealed a prominent monoclonal spike in the gamma region (2.9 g/dL), associated with increased total serum proteins (91 g/L; range 64-82 g/L), elevated IgA levels (20.0 g/L; range 0.4-3.5 g/L), and a markedly abnormal κ/λ FLC ratio (54.00; range 0.31-1.56). Bone marrow analysis demonstrated >18% plasma cell infiltration, confirming the diagnosis of IgA-κ MM. The patient underwent standard therapy followed by autologous stem cell transplantation, achieving disease remission. Conclusions: This case highlights that clinically relevant monoclonal gammopathies may arise rapidly in the absence of classical diagnostic features. Routine SPE represents a cost-effective and accessible screening tool that can identify subtle protein abnormalities, prompting the timely use of more specific and invasive diagnostic procedures for aggressive plasma cell disorders.

Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon. CHIP is prevalent in multiple myeloma (MM) patients, and several lines of investigations suggest it might be relevant for MM pathogenesis and clinical course. Phylogenetic studies indicate that CHIP and MM do not share a clonal origin. CHIP does not consistently affect survival in MM. However, CHIP has been associated with increased treatment-related toxicities. Recent single-cell RNA sequencing data suggest that CHIP is associated with a more inflammatory and immunosuppressive tumor microenvironment (TME), characterized by dysfunctional myeloid and T cells. Furthermore, growing evidence highlights how anti-MM therapies such as alkylators and immunomodulatory drugs can favor the expansion of pre-existing mutant clones. Collectively, these data suggest a bidirectional interplay in which CHIP, acting as a modifier of the TME, may amplify inflammation driven by MM plasma cells and therapy, ultimately affecting MM progression and therapeutic response, while treatment pressure may reshape CHIP clonal architecture. Understanding CHIP dynamics in the context of MM treatment is therefore crucial to optimize therapeutic strategies, anticipate toxicities, and guide tailored approaches. This review summarizes current evidence supporting a translational and clinical impact of CHIP in MM.

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the mainstay of treatment, but due to toxicities and contraindications in renal impairment, denosumab-a monoclonal antibody targeting the RANKL-RANK axis, given once per month-may have become the treatment of choice, especially with three biosimilars being approved, yet adverse events may be troublesome. Furthermore, it seems that anti-MM-directed therapy has an impact on bone turnover, yet the results are premature. However, despite basic research unraveling novel targets such as micro ribonucleic acids, translational research and randomized clinical trials are lagging behind, making this area an unmet need-despite the fact that precision, risk-adapted, biomarker- and imaging-driven medicine should be a valid clinical goal in this setting.

Bispecific antibodies (BiTEs) have transformed the therapeutic landscape of relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses even in heavily pretreated patients. However, their use carries substantial infectious risk due to immunosuppression, particularly hypogammaglobulinemia, induced by T-cell-redirecting therapy. To define the real-world incidence of grade 3–4 infections, we conducted a systematic review and meta-analysis of retrospective studies including RRMM patients treated with BiTEs currently approved for clinical use. Ten studies encompassing 1,373 patients were analysed using a random-effects model of pooled proportions. The overall rate of grade 3–4 infections was 0.25 (95% CI, 0.22–0.30) after a median follow-up of 8.3 months, with moderate heterogeneity (I²=52.9%). Subgroup analyses showed comparable pooled event rates for teclistamab—anti-CD3/BCMA—(0.26; 95% CI, 0.22–0.31) and talquetamab—anti-CD3/GPRC5D—(0.23; 95% CI, 0.14–0.33). Meta-regression revealed an inverse association between infection rates and mean number of prior therapy lines (p = 0.002) and prior BCMA exposure (p = 0.0019), likely because, in real world setting, clinicians select fitter, immunologically stable patients for BiTEs therapy. In summary, approximately one in four RRMM patients receiving BiTEs experiences severe infection. These findings underscore the need for proactive monitoring and standardized preventive measures, including immunoglobulin replacement, prophylaxis, vaccination, to ensure safe, effective integration of BiTEs into routine MM care. The online version contains supplementary material available at 10.1007/s00277-026-07026-9.

We report the first bacteremia case caused by CO₂-dependent methicillin-resistant Staphylococcus epidermidis (MRSE). Blood cultures from a symptomatic multiple myeloma patient yielded Gram-positive cocci. Molecular testing (BioFire FilmArray Blood Culture Identification 2 Panel) identified S. epidermidis with positive mecA/C. However, subculturing failed under ambient air, yielding colonies only under 5% CO₂. Using the MicroScan WalkAway 40 plus system (Pos Combo 1 J panel) in ambient air misidentified the isolate as Micrococcus sp. and produced indeterminate antimicrobial susceptibility testing (AST) results due to insufficient growth. Conversely, testing under 5% CO₂ correctly identified MRSE, matching molecular findings; final species identification was confirmed using the MALDI Biotyper. Furthermore, the same CO₂-dependent isolate was also recovered from a surgical site fluid accumulation following posterior spinal fusion. This case highlights the importance of considering CO₂ dependence for accurate identification and AST of S. epidermidis, especially when initial cultures or automated systems yield inconclusive or erroneous results.

The optimal role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma (MM) remains uncertain particularly in the context of modern induction regimens and emerging immune-based therapies. We compared long-term outcomes of allo-SCT versus autologous SCT (ASCT) in a large single-center cohort. In this retrospective study, conducted at a single center, 1,342 MM patients underwent transplantation between 1992 and 2022 (1,226 ASCT; 116 allo-SCT), with inherent differences in age and transplant eligibility between groups. Median follow-up was 101 months. Outcomes included overall survival (OS), progression-free survival (PFS), relapse incidence, and non-relapse mortality (NRM). Ten-year OS was comparable between ASCT and allo-SCT groups (59.2% vs. 64.0%; p&#x2009;=&#x2009;0.38). However, allo-SCT conferred superior PFS (50.6% vs. 26.0%; p&#x2009;=&#x2009;0.002), driven by a markedly lower relapse incidence (32.5% vs. 68.7%; p&#x2009;<&#x2009;0.001). This benefit was offset by higher NRM with allo-SCT (23.4% vs. 12.9%; p&#x2009;<&#x2009;0.001). Baseline laboratory markers, including elevated LDH and hypoalbuminemia, were associated with relapse and non-relapse mortality, respectively. Allo-SCT offers durable disease control but is limited by treatment-related toxicity. ASCT remains the standard of care, while allo-SCT should be reserved for selected high-risk patients.

Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are biologically distinct hematologic malignancies with heterogeneous clinical courses, and minimally invasive molecular biomarkers are needed to support blood-based discrimination. We performed a comprehensive in silico analysis to derive cross-cohort, direction-consistent transcriptomic programs for CLL and MM and to nominate regulatory microRNAs (miRNAs) linked to these signatures. Public gene-expression datasets from the NCBI Gene Expression Omnibus (two cohorts per disease) were processed with a reproducible workflow to define disease-biased consensus gene sets. Experimentally validated miRNA-target interactions from miRTarBase were integrated with consensus genes for miRNA target over-representation analysis, and miRNA-mRNA networks were constructed to prioritize candidate miRNAs by connectivity. A strict intersection strategy yielded a large, direction-consistent CLL consensus program, whereas a vote-based approach produced a smaller MM program due to a weaker signal in one cohort. Enrichment and network analyses identified compact regulatory modules in CLL, including a highly connected candidate miRNA linked to many CLL-up genes. This framework provides reproducible disease-biased gene programs and evidence-anchored miRNA candidates to support targeted experimental validation and the development of hypothesis-driven blood-based biomarker studies for differential diagnosis and monitoring.

Teclistamab, a B-cell maturation antigen (BCMA) &#xd7; CD3 bispecific T-cell engager, has shown significant efficacy in patients with refractory multiple myeloma (MM). However, the clinical characteristics and optimal management strategies for localized cytokine release syndrome (CRS) remain poorly defined compared with systemic CRS. We report the case of a 57-year-old woman with refractory MM who developed both systemic and localized CRS following teclistamab therapy. She initially presented with grade 3 systemic CRS during step-up dosing phase, which partially resolved with intravenous methylprednisolone. However, interleukin-6 remained elevated in pleural effusions but not in serum, indicating localized pleural cavity CRS. Management with pleural fluid drainage combined with intrapleural dexamethasone successfully controlled the localized CRS. At two months, the patient achieved a partial response and continued teclistamab therapy. To our knowledge, this is among the first reported cases of teclistamab-associated localized pleural cavity CRS effectively managed with intrapleural dexamethasone.

Venous thromboembolism is a major complication in patients with multiple myeloma (MM), with treatment strategies further increasing thrombotic risk. Conventional coagulation tests (CCT) fail to reflect the in vivo hemostatic balance, whereas thrombin generation assay (TGA) provides a global assessment of thrombin dynamics and may better identify hypercoagulable states in MM. To this aim, to evaluated thrombin generation, we enrolled 20 MM patients during follow-up while receiving active MM-treatment: sixteen had immunoglobulin G (IgG) MM, one immunoglobulin A (IgA) MM, one light-chain MM, and two biclonal MM (IgG and IgA). Citrated blood samples were collected under standardized conditions for CCT and TGA. Thrombin generation was measured in platelet poor plasma, both in the absence and presence of thrombomodulin (TM) using the ST Genesia system. TGA revealed increased peak height (139.75%; r.v. 40-69%), endogenous thrombin potential (107.80%; r.v. 58-78%), and velocity index (153.10%; r.v. 31-62%), along with shortened time to peak (ratio 1.04; r.v. 1.2-1.5). Notably, TM-mediated inhibition of thrombin generation was reduced (16.20%; r.v. 60-76%), indicating protein C pathway dysfunction despite preserved natural anticoagulant levels. This procoagulant state was further supported by elevated fibrinogen and D-dimer, together with increased factor VIII and von Willebrand levels. Our findings confirm a hypercoagulable state in MM patients, likely related to endothelial injury and systemic inflammation. Impairment of the protein C pathway, as highlighted by TGA, further contributes to this imbalance. In light of the limitations of prothrombin time and activated partial thromboplastin time, TGA provides a more sensitive and informative evaluation of coagulation dynamics in MM patients.