Yuhuan Zheng

Chidamide is an oral histone deacetylase inhibitor whose use as early maintenance after allogeneic hematopoietic stem cell transplantation (HSCT) remains insufficiently defined. This prospective single‐center Phase 1/2 cohort included all 47 patients enrolled and treated by March 31, 2026. The Phase 2 primary endpoint was 2‐year leukemia‐free survival (LFS). An exploratory observational comparison used 23 platform‐compatible historical comparators, time‐dependent maintenance exposure, and propensity‐score overlap weighting. Both cohorts received chidamide‐containing conditioning. No formal multiplicity adjustment was applied. Treated‐cohort 2‐year LFS was 78.6% (95% confidence interval [CI], 63.9%–87.9%). In the main weighted model, maintenance exposure was associated with lower hazards of death (hazard ratio [HR], 0.29; 95% CI, 0.09–0.96) and relapse or death (HR, 0.24; 95% CI, 0.09–0.63). LFS associations were more consistent across sensitivity analyses; overall survival was less stable in landmark analyses. Graft‐versus‐host disease‐free/relapse‐free survival remained inconclusive. Maintenance began a median of 16 days after HSCT; 45 of 47 patients reached 20 mg twice weekly, and 35 completed 365 days. Grade 3–4 treatment‐emergent adverse events were documented in 37 patients, predominantly cytopenias. One patient died during maintenance from infection with transplant‐associated thrombotic microangiopathy; the relationship to chidamide was not determined. Relapse, non‐relapse mortality, and lymphocyte subset recovery were descriptive. Maintenance was deliverable with active dose management. Trail Registration: ClinicalTrials.gov identifier: NCT05682755

Multiple myeloma (MM) is an incurable malignancy and ranks as the second most common hematological cancer in western countries. Relapsed disease is common in MM patients, and is largely influenced by the establishment of an immunosuppressive tumor microenvironment (TME) and concomitant systemic immune impairment. Myeloid-derived suppressor cells (MDSCs) are crucial regulators of immune homeostasis and response in various pathological states, including cancer. Within the TME, MDSCs and tumor cells engage in bidirectional crosstalk through both direct and indirect mechanisms, collectively driving immune evasion and tumor progression. As a principal immunosuppressive population within the MM milieu, MDSCs play a central role in the immunoregulation of MM. Although immunotherapy has emerged as a pivotal treatment modality for MM, MDSCs, the key constituents of the TME, constitute a major source of resistance to such therapies. This review elucidates the mechanisms governing MDSCs interactions within the myeloma TME, discusses potential therapeutic strategies targeting MDSCs, and outlines a rational framework for integrating MDSC-directed approaches with current MM therapies and immunotherapy.

Multiple myeloma (MM) is an incurable tumor of malignant plasma cells. Importin α4, also known as KPNA3, is a component of the importin α/β system, which contributes to the cytosol-to-nucleus trafficking of cellular substances. In this study, we discovered that KPNA3 was highly expressed in MM and that its expression level inversely correlated with patient prognosis. Both in vitro and in vivo experiments demonstrated that the knockdown of KPNA3 inhibited the proliferation of MM cells, promoted their apoptosis and increased their drug sensitivity. Mechanistic investigations also revealed that the knockdown of KPNA3 inhibited ALDH2 transcription and downregulated the activity of the hedgehog pathway. Additionally, we demonstrated the direct binding of ivermectin (IVM) to KPNA3, a functional component of the importin α/β system. IVM can significantly reduce KPNA3 protein levels and promote apoptosis in MM cells. Finally, both in vitro and in vivo experiments revealed that IVM and selinexor exhibited synergistic anti-MM activities. Overall, our study reveals the role of KPNA3 in MM and suggests that targeting its nuclear import is a promising MM treatment.

Multiple Myeloma bone disease (MMBD) is highly prevalent in the multiple myeloma (MM) patients. Using the patients’ gene expression profile, we ident

Background: Previous studies mainly focused on renal impairment (RI) at multiple myeloma (MM) diagnosis, with few investigating new‐onset RI post‐MM diagnosis. This study aims to indicate the incidence, clinical characteristics and predictive value of new‐onset RI in MM patients. Methods: We conducted a multicenter, retrospective cohort study including 1953 newly diagnosed MM patients from West China Hospital from July 1, 2008, to February 30, 2024 and the international MMRF‐CoMMpass database. Among them, 1770 patients received novel therapeutic agents including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) as first‐line therapy. RI was defined as serum creatinine higher than 2 mg/dL or impaired creatinine clearance (< 40 mL/min/1.73m ² ). The association between new‐onset RI and mortality risk was investigated by Kaplan–Meier analysis and Cox proportional hazard models. Results: Of the cohort, 16.6% developed new‐onset RI, with the majority (67.1%) occurring within 2 years post‐MM diagnosis. The median overall survival (OS) was significantly shorter in new‐onset RI than in those without RI (68 vs. 122 months, p < 0.001). New‐onset RI was an independent risk factor for mortality (HR 1.55, 95% CI 1.28–1.88, p < 0.001), and earlier onset of RI was associated with a higher mortality risk. Moreover, patients with recovery of renal function had prolonged OS compared to those without recovery (95 vs. 64.8 months, p = 0.01). Older age, higher stage of the international stage system (ISS) and RI at diagnosis seemed to be risk factors for new‐onset RI, while first‐line therapy with PIs and IMiDs combinations was associated with a lower risk of RI development (HR 0.69, 95% CI 0.51–0.94, p = 0.017). Conclusions: In conclusion, the incidence of new‐onset RI is high in MM, and is a significant risk factor for mortality, posing a substantial threat to MM patients. Early identification of high‐risk patients for new‐onset RI and prompt preventive strategies is critical for improving MM prognosis. Trial Registration: This study was registered by the Chinese Clinical Trial Registry (ChiCTR2400081476, https://www.chictr.org.cn )

Studies on multiple myeloma (MM), the second most common hematologic malignancy, have shown inconclusive results regarding the role of exercise in treatment. This study evaluated the relationship between physical exercise and MM treatment outcomes. In the 5T‐MM mouse model, tumor‐bearing mice underwent treatment that included bortezomib and dexamethasone alongside 6 weeks of low‐ or moderate‐intensity treadmill aerobic training. Tumor burden and survival data were recorded. Additionally, a retrospective analysis was conducted on 65 MM patients undergoing maintenance therapy at West China Hospital from 2013 to 2024. Patients were categorized based on their adherence to the World Health Organization (WHO) physical activity guidelines, and progression‐free survival and progression‐free survival in maintenance therapy were analyzed. In the mouse model, the combination of dual‐drug therapy and exercise improved outcomes, extending survival by more than 10 days. Aerobic exercises reduced regulatory T cells and increased NK cells in the peripheral blood of mice. In the exercise group of mice, myokines IL‐15 and irisin were up‐regulated, implying both myokines could contribute to the regulation of anti‐MM immunity. In the patient study, patients who met the WHO physical activity recommendations demonstrated significantly better progression‐free survival (PFS) and progression‐free survival in maintenance treatment (PFSm). Overall, appropriate aerobic exercises may benefit some MM patients, suggesting a potential for exercise as an adjunct in MM treatment.

Background Extramedullary disease (EMD) in multiple myeloma (MM) remains a critical clinical challenge due to its aggressive behavior and resistance to conventional therapies. While cytogenetic abnormalities are recognized contributors to MM progression, their specific roles in EMD pathogenesis—particularly in distinguishing bone marrowderived profiles between EMD and non-EMD patients—remain inadequately characterized. Methods In this comprehensive study, we analyzed 41 published studies involving 9424 MM patients, and identified EMD in 32.2% (3038) of cases. Our aim was to elucidate the bone marrow-derived cytogenetic profiles of MM patients with EMD, comparing them to those without EMD. Results Among EMD-MM patients, the most prevalent abnormalities were del(13q)/del RB1 (32.3%), 1q21+ (29.6%), and hyperdiploidy (26.3%). High-risk cytogenetic abnormalities were led by 1q21+ (29.6%), del(17p)/del p53 (14.4%), and t(4;14) (13.6%). Notably, 1q21+ was the most frequent aberration in the EM-E subgroup, accounting for 32.2% of cases. Comparative analyses revealed significantly higher frequencies of del(17p)/del p53 and del(13q)/del RB1 in EMD patients compared to non-EMD patients, along with a slightly higher frequency of 1q21+. Conversely, EMD patients exhibited lower frequencies of hyperdiploidy and t(11;14) promoting MM evolution. Subgroup analyses confirmed these trends and revealed a more pronounced prevalence of del(13q)/del RB1 in the EM-E subgroup. Conclusions Our findings underscore the importance of integrating cytogenetic data into risk stratification for MM patients with EMD. These results also highlight the need for further research to elucidate the mechanisms underlying cytogenetic abnormalities in EMD and their clinical implications.

Mesangial cells (MCs) are stromal cells located in the middle space of the glomerulus, with pivotal functions in glomerular homeostasis. Methods for isolating, purifying, and culturing glomerular MCs have been developed and optimized since the 1980s for use in biomedical research, particularly in the field of nephrology. Mice are the most frequently used experimental animal models in research on renal diseases. In this study, we developed an optimized protocol for murine MCs isolation and ex vivo cell culture. These cells can be passaged multiple times, frozen, revived, and cultured without compromising cell growth or protein expression. This optimized approach significantly reduces the study duration for researchers and enables long-term cell preservation. The necessary equipment for the procedures is easily accessible in a basic biomedical laboratory, and the procedural steps are straightforward. The acquisition of target cells requires only 2-3 weeks, a reduction of at least 1 week compared to existing methods.