POEMS syndrome is a rare paraneoplastic disorder driven by clonal plasma cell proliferation and systemic inflammation, but existing prognostic models inadequately incorporate inflammation-related parameters. The neutrophil-to-lymphocyte ratio (NLR)—a simple, accessible marker of systemic inflammation and immune status—lacks systematic prognostic validation in POEMS syndrome. This single-center retrospective study enrolled 61 patients. The cohort was stratified into two eras (2010–2017 and 2018–2025) to assess temporal consistency. Receiver operating characteristic analysis was used to derive an exploratory NLR cut-off for overall survival. Kaplan–Meier curves and Cox proportional hazards regression were used to assess associations between NLR and progression-free survival (PFS), overall survival (OS), and independent prognostic significance. The effect modification by Li’s prognostic risk strata was explored using interaction and stratified analyses. Correlations were tested by Spearman’s coefficient between NLR and C-reactive protein (CRP), and AUCs were compared by DeLong’s test. ROC analysis showed moderate discrimination of baseline NLR for OS (AUC 0.736, 95

Summary While minimal residual disease (MRD) is a well‐recognized prognostic marker in multiple myeloma (MM), the clinical significance of dynamic MRD trajectories and MRD‐driven therapies remains incompletely elucidated. This retrospective study analysed serial MRD results from 231 newly diagnosed multiple myeloma (NDMM) patients who achieved ≥ complete remission (CR). MRD negativity independently predicted superior progression‐free survival (PFS) (hazard ratio [HR] = 0.222; 95% confidence interval [CI] 0.124–0.400, p < 0.001) and overall survival (OS) (HR = 0.280; 95% CI 0.097–0.809, p = 0.019). Sustaining MRD negativity for ≥6 months improved OS ( p < 0.001), while negativity duration ≥12 months conferred dual prognostic benefits for both PFS and OS (both p < 0.001). Patients with late MRD conversion (after ≥12 months of negativity) had OS comparable to those with sustained negativity ( p = 0.339). Elevated circulating plasma cell at diagnosis (HR = 3.761; 95% CI 1.225–11.550, p = 0.021), failure to achieve MRD negativity post‐induction (HR = 2.886; 95% CI 1.065–7.819, p = 0.037), and a high abnormal PC/BMPC% at MRD conversion (HR = 4.091; 95% CI 1.429–11.701, p = 0.009) were independent risk factors for progression post‐conversion. These findings demonstrate the prognostic significance of sustained MRD negativity and support serial MRD monitoring as a potential basis for individualized MRD‐driven treatment strategies in NDMM.

BACKGROUND:Cytogenetic abnormalities (CAs) in multiple myeloma (MM) are traditionally assessed statically at diagnosis, but longitudinal monitoring reveals dynamic clonal evolution, particularly during relapse. In Asian populations, data on CA dynamics and their prognostic impact remain scarce. PATIENTS AND METHODS:This retrospective study included 106 MM patients (2014-2024) in whom CAs were evaluated at diagnosis and relapse via cIg-FISH. The prognostic impact of clonal burden, copy number alterations, and longitudinal evolution of cytogenetic complexity was comprehensively assessed. RESULTS:At first relapse, 33.0% of patients acquired new CAs, with 1q21+ and del(17p13) incidences significantly increasing (P = .032, P = .003). Longitudinal analysis showed 1q21 amplification (≥4 copies) expanded (27.4%-40.6%), while gain (3 copies) remained stable. Baseline 1q21 amplification predicted shorter 1st PFS (P = .002), whereas 1q21 gain at relapse correlated with inferior 2nd PFS (P = .023), often co-occurring with del(17p13) (28.1%). Persistent 1q21+ and de novo del(17p13) both predicted inferior OS (P < .05). Based on clonal dynamics, patients with >20% expansion exhibited significantly shorter 1st PFS (P = .045) compared to the stable (unchanged) CAs subgroup. Similarly, those acquiring new CAs had shorter 2nd PFS (P = .039) and a trend toward worse OS (P = .056). CONCLUSION:Both acquisition of new CAs and expansion of existing clones at relapse are key prognostic indicators, highlighting the importance of dynamic CA monitoring in MM management.

Extramedullary disease (EMD) at diagnosis confers a poor prognosis in newly diagnosed multiple myeloma (NDMM). This multicenter, open-label, single-arm phase II investigator-initiated trial evaluated selinexor combined with bortezomib, lenalidomide, and dexamethasone (SVRD) in NDMM with EMD. Between October 17, 2022 and November 27, 2025, 30 patients were enrolled; 29 treated patients formed the modified intention-to-treat (mITT) and safety populations (median age 60 years). Induction comprised four 28-day SVRD cycles with protocol-specified consolidation/maintenance and optional ASCT. The primary endpoint was best overall response rate (ORR) during induction per IMWG; patients without a post-baseline assessment were imputed non-responders. In the mITT cohort, ORR was 89.7% (sCR 58.6%, CR 3.4%, VGPR 10.3%, PR 17.2%). Imaging documented EMD regression in 89.7% (complete resolution 79.3%, partial 10.3%); 12-month PFS and OS rates were 87.9% and 96.3%, respectively (medians not reached; median follow-up 18 months). High-risk cytogenetics were present in 31.0%, and 27.6% met ultra-high-risk (“double-hit”) criteria. Grade ≥3 treatment-emergent adverse events occurred in 37.3% patients, most commonly thrombocytopenia (24.1%), neutropenia (6.9%), and pneumonia (10.3%); no treatment-related deaths occurred. SVRD produced deep hematologic responses and high EMD clearance with manageable toxicity, enabling ASCT in 51.7%. These findings support SVRD as a rational frontline option for EMD-positive NDMM and justify randomized studies to confirm durability and benchmark against contemporary quadruplets and cellular therapies. NCT# NCT05900882

ABSTRACT Background Multiple myeloma (MM) is a hematological malignancy associated with poor prognosis. Prognostic prediction based on patient fitness may facilitate the optimization of therapeutic strategies. This study aimed to explore the prognostic significance of sarcopenia, the prognostic nutritional index (PNI) and the controlling nutritional status (CONUT) on the survival of patients with MM. Methods A retrospective analysis was conducted on patients with newly diagnosed MM (NDMM) at Jiangsu Province Hospital between January 2016 and December 2022. Skeletal muscle mass was measured using CT images at diagnosis and normalized for stature to calculate the skeletal muscle index (SMI). Patients with low SMI were defined as sarcopenic. Thresholds for sarcopenia, PNI and CONUT score were determined using X‐tile plot, and participants were categorized accordingly. The Kaplan–Meier survival analysis was used to evaluate the relationship between these indicators and prognosis. Independent prognostic predictors of overall survival (OS) were identified using the multivariate Cox regression model. Results This study included 214 patients diagnosed with NDMM with a median age of 61.7 ± 9.3 years, of whom 87 (40.7%) were female. Sarcopenia was identified in 80 patients (37.4%), with a higher prevalence in women (p = 0.015), those aged over 65 years (p = 0.013) and patients with a BMI ≤ 24 kg/m2 (p < 0.001). Patients with sarcopenia exhibited shorter progression‐free survival (PFS, p = 0.0497) and OS (p < 0.0001). Survival curves revealed that low PNI and high CONUT score were significantly correlated with adverse PFS and OS (all p < 0.05). A combined model incorporating sarcopenia, PNI and CONUT score demonstrated a strong association with PFS (p = 0.0007) and OS (p < 0.0001), and patients with concurrent sarcopenia, low PNI and high CONUT score exhibited the poorest survival rates. Multivariate Cox analysis indicated that sarcopenia was a significant and independent predictor of shorter OS (hazard ratio [HR] = 2.748, 95% confidence interval [CI]: 1.495–5.052, p = 0.001) in patients with NDMM. Conclusions Sarcopenia is an independent prognostic indicator of OS in patients with NDMM. The integration of PNI and CONUT scores provides a comprehensive prognostic model for prognosis in patients with MM, highlighting the importance of functional status and nutritional assessments in clinical management.

Multiple myeloma (MM) remains a challenging hematological malignancy, with outcomes varying widely due to genetic heterogeneity. Among the cytogenetic abnormalities, deletion of the short arm of chromosome 17 (del(17p)) stands out as an important high-risk feature influencing prognosis. Del17p often involves the loss of the TP53 gene at 17p13.1 locus, a key tumor suppressor, however the impact of loss of multiple other genes on 17p on tumor cell behavior is still unclear. Evidence from studies indicates that the size of the deletion and the number of affected genes correlate with worse outcomes, highlighting a multifactorial impact that extends beyond TP53. In this study, using Molecular Alteration of Chromosomes with Engineered Tandem Elements (MACHETE) method, we induced del17p by creating a 21-Mb deletion of the short arm of chromosome 17 in the wild-type AMO1 cell line. This was followed by single-cell clone selection and expansion. The successful deletion of the 17p arm was confirmed in three single-cell expanded cultures through ultra-low pass sequencing and fluorescence in situ hybridization (FISH) for 17p, with deep whole-genome sequencing (WGS) further validating the 17p deletion breakpoint. Transcriptomic analysis revealed that 83% of genes located on the 17p arm were significantly downregulated (padj < 0.05) compared to parental cells. We next observed that del17p cells exhibit comparable proliferation rates to parental cells but demonstrate enhanced clonogenic potential, increased invasion capacity, and greater resistance to proteasome inhibitors. To determine which gene drives the phenotypic effects of del17p, we analyzed transcriptomic data from del17p patient cells across three independent datasets to identify genes on the 17p locus that are consistently downregulated in patients with del17p MM. By combining these findings with transcriptomic data from our isogenic line, we pinpointed a core group of 14 genes within the 17p locus that are consistently downregulated in del17p cells and reside within the minimal deleted region. Notably, reduced expression of SAT2 stood out as being specifically linked to worse patient outcomes. Functional studies further demonstrated that reintroducing SAT2 into 17p-deleted cell lines counteracts the enhanced clonogenic potential driven by 17p loss, suggesting that SAT2 plays a critical role in modulating the aggressive behavior of del17p cells. In conclusion, our induced del17p cell line using MACHETE technique provides ability to attain new insights into the molecular mechanisms underlying del17p-associated phenotypes and identifies SAT2 as one of the key genes within the 17p locus that contributes to the phenotypic effects of del17p.

Autologous stem cell transplantation (ASCT) remains central in multiple myeloma, yet the optimal CD34+ infusion dose is uncertain. We retrospectively analyzed 176 newly diagnosed patients undergoing ASCT. Survival was estimated by Kaplan-Meier, and predictors were assessed by Cox regression. Among ASCT patients, a high CD34+ dose (≥5 × 106/kg) was associated with superior progression-free survival (PFS, p = 0.020), OS (p < 0.001), deeper responses (p = 0.034), and sustained minimal residual disease (MRD) negativity (p = 0.001). High dose correlated with oligoclonal bands formation (OB, p = 0.038), indicating immune reconstitution. Patients exhibiting both high CD34+ dose and OB constituted the best OS (p < 0.001). In multivariate analysis, CD34+ ≥5 × 106/kg independently predicted superior PFS (p = 0.014) and OS (p < 0.001). In sum, CD34+ ≥5 × 106/kg is a practical dosing target that couples immune reconstitution via OB formation to durable post-ASCT survival, with no incremental benefit above 10.64 × 106/kg.

Equecabtagene Autoleucel (Eque-cel, IASO Bio), as a fully human BCMA chimeric antigen receptor (CAR) T-cell therapy, received approval in China for patients (pts) who had underwent at least three prior lines of therapy in June 2023. Since Mar 2022, researchers have been conducting the study to evaluate the efficacy and safety of Eque-cel in the treatment of transplant-ineligible pts with high-risk newly diagnosed MM (NDMM). Here we report the promising efficacy and safety profiles in FUMANBA-2 study (NCT05181501). FUMANBA-2, a phase 1, multi-center, single-arm clinical study, enrolled NDMM pts with high-risk features (defined as R-ISS stage III, double-hit, or triple-hit per mSMART 3.0 criteria). Pts would undergo 4 cycles of induction chemotherapy based on one of three regimens: Bortezomib-Lenalidomide-Dexamethasone, Bortezomib-Cyclophosphamide-Dexamethasone, or Bortezomib-Adriamycin-Dexamethasone. After the third cycle, the pts who were evaluated not eligible for Autologous Stem Cell Transplant (ASCT) underwent leukapheresis for Eque-cel manufacture. After lymphodepletion with Fludarabine-Cyclophosphamide, pts received a single infusion of Eque-cel at the dose of 1.0 x 106 CAR-T cells/Kg. Primary endpoint was the proportion of minimal residual disease (MRD)-negative (MRD−; sensitivity <10-5) and progression-free survival (PFS). Secondary endpoints included overall response rate, duration of response, safety, pharmacokinetics, and pharmacodynamics. As of May 13, 2025, a total of 16 pts (68.8% male; median aged 58.5 years [range, 51-69]) received Eque-cel infusion. Cytogenetics were detected in all pts with at least one high risk cytogenetic abnormalities (HRCA). 13 pts (81.3%) had double-hit, and 2 pts (12.5%) had triple-hit cytogenetics. 3 pts (18.8%) had R-ISS stage Ⅲ with a double-hit, and one patient (6.3%) had R-ISS stage Ⅲ with a triple-hit. 4 pts (25.0%) had extramedullary disease (EMD). With a median follow-up of 27.04 months (range: 10.8-36.1), all pts achieved at least VGPR with 93.8% (15/16) pts achieved sCR. All 16-pts achieved MRD-negativity within 1-month, and 80% (95% CI: 40.9%, 94.6%) pts achieved sustained MRD negativity over 24 months. The median PFS was not reached (NR). The PFS rates at 12-month, 18-month and 24-month were 87.5% (95%CI: 58.6%, 96.7%), 80.2% (95%CI: 50.1%, 93.2%) and 74.5% (95%CI: 45.4%, 89.6%), respectively. In pts with ≥ 2 HRCAs and EMD, 24-month PFS rates were 76.2% (95% CI:42.7%, 91.7%) and 75.0% (95% CI:12.8%, 96.1%), respectively. The median OS was NR, and OS rate at 24-month was 81.3% (95%CI: 52.5%, 93.5%). All 16-pts experienced treatment-related AEs, the most common of which were cytopenia, pyrexia, and infections. CRS occurred in 11 pts (68.8%), all of which were grade 1-2. The median time to CRS onset was 7 days (range: 2-9 days), with the median duration of 3 days (range: 1-8 days). No neurotoxic effects or ICANS was observed. Hypogammaglobulinemia occurred in 50% (8/16) of pts, and the median time to onset was 24 days (range: 8-79 days), with a median duration of 418 days (range: 22-797 days). The most common serious AEs were infections, which occurred in 7 pts (43.8%), with pneumonia being the most frequently reported (7 pts, 43.8%). Other infections included COVID-19, influenza, and meningitis. The expansion and persistence of Eque-cel in peripheral blood were evaluated in all 16 pts. The median peak vector copy number (VCN Cmax) of Eque-cel was 79681.30 copies/μg gDNA (range, 4519-130258 copies/μg gDNA). The median time to reach Cmax (Tmax) was 10 days (range: 7-21 days). The median area under the curve at day0-28 (AUC0-28d) was 691468.75 Day × Copies/μg DNA (range, 14552-1235359 Day × Copies/μg DNA). The median persistence of Eque-cel in peripheral blood was 75 days (range: 29-283 days) post-infusion. Soluble BCMA was cleared within 1 month post infusion in 81.25% (13/16) of pts. Secretion of inflammatory cytokines was also observed, with median peak levels of 58.59 pg/mL (range: 9.12-3017.83 pg/mL) for IL-6, 44.30 mg/L (range: 3.66-117.30 mg/L) for CRP, and 553.35 ng/mL (range: 68.10-2349.00 ng/mL) for ferritin. In conclusion, the current data suggest that Eque-cel could be a promising and effective treatment option for high-risk NDMM pts following induction therapy. However, longer follow-up and randomized controlled trials are necessary to further clarify the efficacy and safety of Eque-cel in this patient population.

Introduction: POEMS syndrome is a rare clonal plasma cell disorder characterized by complex manifestations, marked heterogeneity, and delayed diagnosis. Its pathogenesis remains poorly understood (Isshiki et al., 2022), particularly regarding the phenotype of clonal plasma cells and their interactions with the immune microenvironment. Existing studies are largely limited to case reports or bulk-tissue analyses, with relatively scarce high-resolution data (Nagao et al., 2019). The immunomodulatory role of neutrophils in POEMS also remains uncharacterized. Single-cell technologies enable in-depth dissection of the immune ecosystem and may uncover novel mechanisms and therapeutic targets. Methods: Bone marrow samples from 9 POEMS and 7 monoclonal gammopathy of undetermined significance (MGUS) patients—including paired pre/post-treatment samples from 3 POEMS cases—underwent single-cell RNA sequencing (scRNA-seq). Analyses included marker identification, differential expression, GO/KEGG/GSVA enrichment, pseudotime trajectory, CellPhoneDB-mediated interaction, and UCell immune scoring. SCENIC identified neutrophil-specific transcription factors. KLF5 expression was validated by Western blot (WB). HL-60 cells were differentiated into neutrophil-like cells (dHL-60) and transduced for KLF5 overexpression or inhibited pharmacologically. Functional assays (CCK-8, Transwell, flow cytometry, WB, ELISA, immunofluorescence) assessed proliferation, migration, apoptosis, cytokine secretion, and NETs formation. NETs from KLF5-overexpressing dHL-60 cells were co-cultured with plasma cell lines (RPMI-8226, U266) to evaluate effects on proliferation, migration, vascular endothelial growth factor (VEGF) production, and tumorigenicity. Results: (1) Clonal plasma cells: scRNA-seq identified a unique cluster with MHC-IIlowSPP1highIGLV1-40highIGKV1-5highIGHV1-24high expression, marked by elevated metabolism and inflammatory signaling implicated in multisystem damage. (2) Immune microenvironment: Neutrophils were enriched and expressed VEGF, indicating roles in angiogenesis and immune suppression. Macrophages exhibited exhaustion with impaired antitumor function. Post-treatment samples showed reduced neutrophil abundance and partial immune recovery. (3) KLF5 activity in neutrophils: SCENIC identified KLF5 as a key transcription factor. Its expression was elevated in POEMS bone marrow (p = 0.0109). In vitro, KLF5 promoted dHL-60 proliferation (p = 0.0025), migration, VEGF (p = 0.0018), and IL-10 (p = 0.0019) secretion, suppressed apoptosis (p = 0.0049), and reduced IL-6 (p = 0.0120) and TNF-α (p = 0.0861). NETs formation was enhanced (p = 0.0077), and all effects were reversed by KLF5 inhibition (ML264). (4) NETs-mediated modulation of plasma cells: scRNA-seq of post-treatment plasma cells revealed downregulation of neutrophil activation and NETs-related pathways. NETs co-culture promoted plasma cell proliferation, migration, VEGF production and tumorigenicity, all of which were abrogated by DNase I. Conclusions: This study delineates the single-cell immune landscape of POEMS syndrome, identifying a clonally expanded plasma cell subset with distinct molecular and metabolic features. It reveals a neutrophil-driven immunosuppressive microenvironment, in which KLF5 enhances neutrophil function, VEGF production, and NETs release, thereby promoting plasma cell malignancy. The “KLF5–neutrophil–plasma cell” axis provides novel mechanistic insight into POEMS pathogenesis.

Background:Solitary plasmacytoma (SP) is a rare plasmacytoma. Research on clinical characteristics and prognostic factors for SP is very limited. Objective:This study aimed to evaluate the clinical attributes and prognostic indicators for individuals afflicted with SP. Design:We retrospectively analyzed the clinical parameters and survival data of 49 patients diagnosed with SP from three centers between the year 2009 and 2024. Methods:The Kaplan-Meier curves were constructed to compare the survival outcomes. The independent risk factors were determined based on the Cox proportional hazards model. Results:Among the 49 patients with SP, 30 (61.2%) were classified as solitary bone plasmacytoma (SBP), while 19 (38.8%) had solitary extramedullary plasmacytoma (SEP). Anatomically, SEPs predominantly localized to the upper aerodigestive tract (47.4%), whereas SBPs exhibited a predilection for the axial spine (30.0%) and appendicular long bones (20.0%). Survival analysis revealed significantly reduced progression-free survival (PFS) in the SBP cohort compared to SEP patients (p = 0.0002), though no statistically significant difference in overall survival was observed between groups (p = 0.1012). Radiotherapy in conjunction with surgery or chemotherapy did not substantially enhance the outcome of the patients with SP. Multivariate Cox regression analysis identified SBP subtype (hazard ratio (HR) = 0.068, 95% confidence interval (CI): 0.008-0.537, p = 0.011) and elevated Ki67 expression (HR = 4.545, 95% CI: 1.005-20.542, p = 0.049) as independent prognostic factors for inferior PFS. Notably, SBP patients with Ki67 expression exceeding 35% demonstrated the poorest clinical outcomes. Conclusion:The prognosis of patients with SBP was poorer than that with SEP. Patients with SBP exhibiting Ki67 expression exceeding 35% had the poorest outcome.

OBJECTIVE:To analyze the prognostic value of del(1p32) in patients with newly diagnosed multiple myeloma (MM). METHODS:The clinical data of 341 newly diagnosed MM attended in Jiangsu Province Hospital were retrospective analyzed. Clinical characteristic combined with genetic features, especially del(1p32), were analyzed for survival and prognostic of patients. RESULTS:Among the 341 patients with newly diagnosed MM, 24(7.0%) patients were del(1p32) positive. The progression-free survival (PFS) and overall survival (OS) were significantly shorter in MM patients with del(1p32) than those without del(1p32) (PFS: P < 0.001;OS: P < 0.001). The COX proportional-hazards model showed that del (1p32) was an independent risk factor for PFS and OS of patients with MM. The patients with both 1q21 gain/amplification and del(1p32), as "double-hit chromosome 1", have worse prognosis than those with only 1q21 gain/amplification or only del(1p32) (PFS: P < 0.001; OS: P < 0.001). CONCLUSION:Del(1p32) is an independent risk factor for PFS and OS of patients with MM. Del(1p32) detection should be widely used in the prognostic analysis for newly diagnosed MM patients.

Purpose Elderly patients with newly diagnosed multiple myeloma (NDMM) show heterogeneous outcomes due to their potential risk, and lack of the standard-of-care risk stratification model. In this study, we proposed the prognostic model by analyzing the additive value of geriatric assessment and clinical factors. Patients and Methods The collected individual data from 131 elderly patients(≥65) with NDMM enrolled. An additive scoring system on the basis of top features predicting progression-free survival (PFS) and overall survival (OS) was developed. Results At a median follow-up of 23.7 months, age, ADL, PLT, CRP, CPC had the highest impact on OS and were used to construct OS risk model. Likewise, age, ADL, PLT, CRP, CPC for PFS risk model. A value was assigned to each risk feature according to their OS impact (age>75 5 points, ADL>4 3 points, PLT<100×109/L 4 points, elevated CRP 3 points, CPC≥0.105% 2 points). And for PFS risk model, age>75, CCI ≥2, β2≥3.5mg/L, PLT<100×109/L and CPC≥0.105% were assigned 2, 2, 3, 2, 2 points repectively. Patients were stratified into three risk groups according to the total additive score. Median OS was not reached versus NR versus 54 versus 56 months, and median PFS was NR versus 47 versus 23 months, respectively. Nomogram was also constructed using the same variables. the AUC values obtained from our nomogram were 0.742, 0.773 and 0.807 for predicting the 1-, 2- and 3-year OS rates, respectively, which were higher than those of both the MRP model (0.692, 0.691, 0.683) and IMWG-GA model (0.649, 0.634, 0.659). Additionally, 1-, 2- and 3-year PFS in our cohort yield value of 0.775, 0.782,0.774, respectively, which also exhibited superior performance compared to both the MRP model(0.646, 0.607, and 0.602), and the IMWG-GA model( 0.636, 0.506, and 0.576). Conclusion Our simple prognostic staging system allowing a better stratification of patients with elderly NDMM. The additive geriatric metrics of this score fosters its future implementation with new prognostic variables.

The aim of the study was to evaluate the prognostic impact of minimal residual disease (MRD) in the real-world setting and the interaction between MRD and molecular risk, clinical response and autologous stem-cell transplant (ASCT). A retrospective analysis of 275 newly diagnosed multiple myeloma (NDMM) patients who achieved very good partial remission (VGPR) or better before maintenance were involved. We examined MRD status by multiparameter flow cytometry (MFC). At a median follow-up of 37 months (4–88 months), In patients who achieved ≥ VGPR, those with MRD negativity had significantly longer PFS (51 vs. 26 months; P < 0.001) and OS (Not reached: NR vs. 62 months, P < 0.001) than those with MRD positivity. MRD positivity was the independent prognostic factor for PFS with hazard ratios of 2.650 (95% CI 1.755–4.033, P < 0.001) and OS with hazard ratios of 2.122 (95% CI 1.155–3.899, P = 0.015). Achieving MRD negativity was able to ameliorate a poor prognosis associated with genetic high risk. MRD negativity was associated with better PFS regardless of ASCT treatment. MRD status was more predictable for clinical outcome than conventional clinical responses. Moreover, Sustained MRD negativity ≥ 12 or ≥ 24 months improved both PFS and OS. Patients with NDMM who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes regardless of high-risk cytogenetics, ASCT and clinical responses in a real-world setting.

Low serum cholesterol levels are associated with increased tumor morbidity and mortality. However, the relationship between serum lipid profile and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is still unclear. The aim of our study was to clarify the importance of the serum lipid profile in predicting the severity and prognosis of patients with POEMS syndrome. Forty-three patients with newly diagnosed POEMS syndrome admitted to the Department of Hematology of Jiangsu Provincial People's Hospital between August 2013 and February 2023 were selected. They had explicit serum lipid profiles. There were 27 males and 16 females with a median age of 54 years (range, 28–77 years). Survival curves were plotted using the Kaplan–Meier method, and comparisons between the two groups were performed using the log-rank test. The Cox proportional-hazards model examined risk factors associated with the prognosis of POEMS syndrome. Receiver-operator characteristic (ROC) curves assessed the predictive accuracy. 23 (53.5%) patients had low total cholesterol (TC) levels. Low levels of TC were concerned with unfavorable progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.004), and at the same time, the low circulating TC concentration was an independent risk factor for PFS ( p = 0.020) and OS ( p = 0.011). Low TC values could improve the risk stratification, especially in high-risk patients. In conclusion, low serum TC levels may predict inferior prognosis in patients with POEMS syndrome; in future clinical application, low TC may be a reliable indicator of prognosis.

IntroductionThe emergence of chimeric antigen receptor (CAR)-T therapy targeting B cell maturation antigen (BCMA) has improved the prognosis of patients with multiple myeloma (MM); however, the majority of patients eventually experience relapse.MethodsIn this study, employing the latest single-cell RNA sequencing technology, we examined 24 bone marrow or peripheral blood samples collected throughout the course of anti-BCMA CAR-T therapy, analyzing a total of 59,725 bone marrow cells and 72,479 peripheral blood cells.ResultsOur findings reveal that tumor cells in relapsed patient exhibit higher expression levels of HSP90B1 and HSPA5, and demonstrate significantly enriched pathways regarding endoplasmic reticulum stress and unfolded protein response. In the analysis of T cells, we observed that patient with impaired effector function and increased expression of immune checkpoints in endogenous T cell are more susceptible to relapse. Notably, T cells from both the bone marrow microenvironment and peripheral blood share highly similar biological characteristics.DiscussionOverall, this study provides a comprehensive atlas of endogenous immune cells, particularly in the relatively long term, after CAR-T therapy. It offers clinical evidence for a deeper understanding of the internal environment post CAR-T treatment and for identifying mechanisms underlying relapse.

Introduction Circulating plasma cells (CPC) have been reported to be one of the indicators of high-risk multiple myeloma (MM), yet the prognostic significance of CPC in Chinese population and the genetic mechanisms underlying CPC formation have not been fully elucidated. Methods Patients with newly diagnosed MM were included in this study. We used multi-parameter flow cytometry (MFC) for CPC quantification and next-generation sequencing (NGS) technology for mutational landscape mapping to identify the correlation of CPC level with clinical characteristics and the mutations. Results A total of 301 patients were enrolled in this investigation. We demonstrated that CPC quantification could effectively mirror the tumor load, and CPC ≥ 0.105% at diagnosis or detectable CPC after therapy indicates poor treatment response and adverse outcome, and the introduction of CPC into the R-ISS enables a more accurate risk stratification. Interestingly, we noticed an elevated percentage of light-chain MM in patients with higher CPC. Mutational landscape revealed that patients harboring mutations in TP53, BRAF, DNMT3A, TENT5C, and IL-6/JAK/STAT3 pathway-related genes tended to have higher CPC levels. Gene enrichment analysis demonstrated that pathways involving chromosome regulation and adhesion may be potential mechanisms accounting for CPC formation. Discussion Accordingly, quantification of CPC may provide a less-invasive and reliable approach for identifying high-risk MM in Chinese population.

INTRODUCTION: Extramedullary disease (EMD) is a rare but increasingly recognized complication in newly diagnosed multiple myeloma (NDMM) patients, associated with a poorer prognosis and drug resistance. However, data on treatment outcomes for EMD are primarily based on retrospective studies, necessitating prospective studies with well-defined EMD to assess treatment efficacy and safety accurately. In this context, we present the preliminary findings from a prospective phase 2 study evaluating the safety and efficacy of selinexor in combination with VRd as a first-line treatment for NDMM patients with EMD(NCT05900882). METHODS: The study enrolled NDMM patients under the age of 75 who had measurable extramedullary disease (defined as paraosseous or extramedullary plasmacytoma ≥2cm. Patients received selinexor (60 mg QW) in combination with VRd (SVRD) regimen as induction therapy for 4 cycles (28 days of each cycle). Following the induction phase, patients underwent two cycles of VRd consolidation therapy after autologous stem cell transplantation (ASCT), while those who did not undergo ASCT received another 4 cycles of SVRD consolidation therapy. All pts received bortezomib plus lenalidomide for maintenance for at least 24 months. The primary endpoint of the study was the best response rate during induction therapy, and secondary endpoints included complete response (CR) rate, duration of response (DOR), safety, and survival outcomes. RESULTS: Between Oct 17, 2022 and May 12, 2023, a total of 10 NDMM pts with EMD were enrolled and received treatment at The First Affiliated Hospital of Nanjing Medical University. The median age was 62 years (range 48-70). Among them, 7 patients (70%) had RISS stage II/III disease, 7 patients (70%) were classified as high risk based on the mSMART stratification, and 3 patients (30%) had extra-osseous extramedullary plasmacytomas (EMP) as per Table 1. By the data cut-off date of July 15, 2023, at a median follow-up of 5.5 months (range 2.2-9.3 months), 5 pts completed 4 cycles of SVRd inductive treatment, 2 pts underwent ASCT, 1 pts discontinued the clinical trial due to progressive disease, and 3 pts were now receiving consolidation therapy ( Figure 1). Among the 10 evaluable pts for best serological response, 4 pts (40%) achieved serological CR/sCR, and 6 pts (60%) achieved VGPR. The depth of remission improved with the continuous treatment. Extramedullary disease evaluation in 9 patients showed complete disappearance of extramedullary lesions in 3 patients (30%), partial response in 5 patients (50%), and stable disease in 1 patient (10%). 8 (80%) pts experienced any grade AE. Grade 3 or 4 AEs were reported in 2 pts (9 events in total), with the most common being leukopenia (3), neutropenia (3) and thrombocytopenia (3). Non-hematological AEs were mainly grade 1-2, except for 1 pt with grade 3 anorexia. No pts required dose reductions or discontinuations due to AEs. CONCLUSIONS: The combination of selinexor with VRd regimen demonstrated early, deep, and durable responses in NDMM patients with extramedullary disease, both in serological and extramedullary responses, with a manageable safety profile. These results suggest that this therapeutic intervention holds promise as an effective and well-tolerated treatment option for multiple myeloma patients with EMD. Further studies are warranted to validate these findings and establish the long-term benefits of this combination therapy.