Renal impairment (RI) in multiple myeloma (MM) patients significantly impacts outcomes, yet the prevalence and causes of early mortality within 12 months of diagnosis in newly diagnosed MM (NDMM) with RI are understudied in the novel agent era. This study conducted a nested case-control analysis including 199 NDMM patients with RI from West China Hospital from June 2016 to November 2022. Among this cohort, we identified 19 cases of early mortality (death within 12 months of diagnosis) and selected 76 matched controls from the remaining patients at a 1:4 ratio based on age, gender, and diagnosis date. All controls were followed for over one year. Potential risk factors including elevated N-terminal pro-brain natriuretic peptide (NT-proBNP), heart failure at diagnosis, and other clinical indicators were analyzed. The incidence of early death was determined to be 9.5

Background:Adjuvant therapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is effective and safe for patients with completely resected non-small cell lung cancer (NSCLC) with EGFR mutations, but certain issues remain unresolved. This retrospective study aimed to investigate the optimal adjuvant treatment regimen and duration of EGFR-TKI treatment, evaluate the efficacy of different generations of EGFR-TKIs, and identify prognostic factors for patients with stage N2 EGFR-mutant NSCLC. Methods:From July 31, 2010, to July 31, 2022, clinicopathological data were collected from 190 patients with N2 EGFR-mutant NSCLC who underwent complete surgical resections. Patients received either postoperative adjuvant EGFR-TKI monotherapy or adjuvant combination therapy with EGFR-TKI (chemotherapy, radiotherapy, or radiochemotherapy prior to EGFR-TKI therapy). Overall survival (OS) and disease-free survival (DFS) were assessed. Results:The median follow-up of the 190 patients was 49 months, with a 4-year DFS rate being 41.3% and the 4-year OS rate being 80.2%. Among these patients, 127 (66.8%) received EGFR-TKI monotherapy, while 63 (33.2%) received combination therapy. Pathological tumor-node-metastasis (pTNM) stage (stage IIIA vs. stage IIIB; P=0.01) and generation of EGFR-TKI (third vs. first; P<0.001) were significantly associated with DFS benefit, but not with OS. The number of positive mediastinal lymph nodes (<3 vs. ≥3) correlated with both DFS (P=0.02) and OS (P=0.04) benefit. EGFR mutation status (exon 19 deletion vs. exon 21 L858R point mutation) was significantly associated with DFS (P=0.03) and OS (P=0.01). However, EGFR-TKI monotherapy and combination therapy demonstrated no significant differences in terms of DFS (P=0.73) or OS (P=0.13). Longer duration of EGFR-TKI treatment (>3 vs. ≤3 years) was associated with better DFS (P<0.001) and OS (P<0.001). Moreover, pTNM stage, generation of EGFR-TKI, and duration of EGFR-TKI treatment were identified as independent prognostic factors for DFS (all P<0.05), while duration of EGFR-TKI treatment was also an independent prognostic factor for OS (P<0.001). Conclusions:Our study found that EGFR-TKI monotherapy and combination therapy demonstrated no significant differences in terms of DFS or OS in patients with completely resected stage N2 EGFR-mutant NSCLC. Adjuvant treatment with third-generation EGFR-TKIs and prolonged treatment duration may offer enhanced survival benefits.

Background: Emerging evidence suggests that 1p32 deletion (del(1p32)) may represent an independent high-risk factor in newly diagnosed multiple myeloma (NDMM). However, its clinical significance remains underexplored in large real-world cohorts, particularly among Asian populations. Aims: To investigate the prevalence and prognostic impact of del(1p32) in Chinese patients with NDMM and assess its interaction with other high-risk cytogenetic abnormalities (HR CAs). Methods: A total of 279 NDMM patients with complete clinical and cytogenetic data who underwent FISH testing at West China Hospital from July 2022 to November 2024 were retrospectively analyzed. Patients were stratified based on del(1p32) status and further evaluated for progression-free survival (PFS) and overall survival (OS) using Kaplan–Meier and Cox regression analyses. The presence of co-occurring high-risk abnormalities and transplant status were also considered. Results: Fourteen patients (n=14, 5.0%) harbored del(1p32), with 1 case showing biallelic deletion. The patients harboring del(1p32) demonstrated a higher proportion presenting advanced R-ISS stage III disease (P=0.028) and elevated serum LDH levels (P=0.023). Consistently, they showed significantly shorter PFS (median 21.5 vs. 31.7 months, P<0.05) and OS (median 25.0 vs. 34.0 months, P<0.05) compared to those without the deletion. Notably, the patient with biallelic del(1p32) manifested extremely poor outcomes (PFS and OS both 5.77 months). In patients receiving autologous stem cell transplantation (ASCT), del(1p32) was associated with a trend toward shorter PFS (19.4 vs. 32.1 months, P=0.074). Furthermore, the presence of ≥2 additional high-risk cytogenetic abnormalities (e.g., del(17p), t(4;14), and/or 1q gain/amplification) along with del(1p32) dramatically worsened survival outcomes (mPFS and mOS both 5.77 months), indicating a synergistic adverse effect. Conclusions: Del(1p32) is a rare but adverse prognostic marker in NDMM and retains its predictive value even in the context of ASCT. These findings highlight the need to include del(1p32) in future risk stratification models and explore tailored therapies for affected Asian patients.

In clinical practice, patients with unresectable stage III non‐small cell lung cancer (NSCLC) often exhibit limited tolerance to concurrent chemoradiotherapy (cCRT). This retrospective study evaluated the efficacy and safety of induction chemoimmunotherapy followed by definitive radiotherapy (RT) and consolidation immunotherapy, compared with standard cCRT plus consolidation immunotherapy. A total of 102 patients treated at West China Hospital between June 2019 and June 2024 were analyzed. Primary endpoints were overall survival (OS) and progression‐free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and treatment‐related adverse events (TRAEs). Survival outcomes were comparable between groups (median OS: not reached vs. 36 months, p = 0.52; median PFS: 25 vs. 28 months, p = 0.71), with higher 3‐year OS observed in the induction group (61.4% vs. 38.3%). In the induction group, ORR after systemic therapy was 74.2%, and post‐RT DCR reached 83.3%. TRAEs were comparable across groups, with pneumonitis being the most frequent toxicity and no significant increase in grade ≥3 events observed. These findings support the induction‐based sequential strategy as a viable alternative to cCRT for patients with unresectable stage III NSCLC, especially those unsuitable for concurrent treatment.

OBJECTIVE:To evaluate the clinical and prognostic significance of immunoglobulin heavy chain (IgH) cytogenetic abnormalities in patients with newly diagnosed multiple myeloma (NDMM) and explore their association with other high-risk cytogenetic features. PATIENTS AND METHODS:We retrospectively analyzed 503 NDMM patients treated between February 1, 2016, and February 29, 2024. Cytogenetic abnormalities were identified by fluorescence in situ hybridization. RESULTS:The study uncovered a significant correlation between IgH cytogenetic abnormality and an increased prevalence of anemia (p < 0.001), thrombocytopenia (p = 0.005), and the presence of high-risk cytogenetic aberrations, including +1q21 (p < 0.001) and P53 deletion (p = 0.001). Patients afflicted with IgH cytogenetic abnormality were found to have more advanced stages of the disease, as indicated by higher Disease Stage (p < 0.001), International Staging System (p = 0.018), Revised International Staging System (RISS) (p < 0.001), and Second Revision of the International Staging System (p < 0.001). This cytogenetic abnormality was also linked to a markedly diminished progression-free survival (PFS) across RISS I-II, yet autologous stem cell transplantation (ASCT) offered significant improvement for PFS (p < 0.05). Notably, the specific t(14;16) and t(14; undefined) were significantly associated with shorter PFS (p < 0.001) and shorter overall survival (OS) (p < 0.05). Additionally, the confluence of IgH cytogenetic abnormality with other cytogenetic abnormalities, particularly +1q21, P53 deletion, RB/D13S319 deletion, and elevated LDH level, was found to exacerbate the disease outcome. CONCLUSION:IgH cytogenetic abnormalities indicate aggressive disease and poorer survival in NDMM, especially when accompanied by other high-risk markers. ASCT may mitigate these adverse outcomes, supporting its role in individualized treatment strategies.

Immunotherapy has become the standard treatment for many types of cancers, but an increasing number of patients who initially respond to these treatments develop acquired immunotherapy resistance (AIR). Here, we recapitulated the entire process of immunotherapy from response to AIR in mice with non–small cell lung cancer (NSCLC). With implanted tumor organoids derived from these models and serial transplants, we demonstrated that tumor cell–intrinsic mechanisms contributed significantly to AIR. Single-cell RNA sequencing and electron microscope assays revealed that resistant tumor cell–expressing collagens, including Col3a1 and Col6a1 , formed multiple physical barriers surrounding tumor cells. Disruption of these barriers by collagenase or knockout of both Col3a1 and Col6a1 in tumor cells could sensitize the tumors of AIR. Mechanistically, the TGFβ pathway was upregulated upon immunotherapy, and treatment with TGFβ significantly increased the expression levels of both Col3a1 and Col6a1 in tumor cells. COL3A1 formed a castle-like barrier for a cluster of tumor cells and prevented T cell infiltration, while COL6A1 formed an armor-like barrier surrounding individual tumor cells to protect them against direct T cell attack. Our data reveal a tumor cell–intrinsic mechanism of AIR, mediated by collagen-containing physical barriers, which immediately suggests a clinical treatment option.

Background: Cellular-mesenchymal to epithelial transition factor (c-MET) alterations have significant therapeutic implications in non -small cell lung cancer (NSCLC). Although MET fusion is a rare genomic event, advances in detection technologies have enabled the identification of various MET fusion partner genes. However, standard therapeutic options for MET fusion in NSCLC cases remain undefined. This report presents a novel fusion variant, EML4-MET, encompassing exons 1 to 13 of EML4 and exons 15 to 21 of MET, including the entire MET kinase domain, and discusses the response of this case to savolitinib treatment. Case Presentation: A 65-year-old woman was diagnosed with advanced poorly differentiated lung carcinoma. Molecular profiling of circulating tumor DNA (ctDNA), carried out by next -generation sequencing (NGS), identified a novel EML4-MET fusion. The patient was administered the MET receptor tyrosine kinase inhibitor savolitinib at 400 mg daily. One month later, computed tomography (CT) revealed some lesions with volume reduction. However, COVID-19 diminished the efficacy of savolitinib. Regrettably, the patient succumbed to respiratory and circulatory failure due to disease progression in March 2023. Conclusion: This case uncovers a new type of MET fusion and expands the range of potential MET fusion targets in NSCLC. The patient responded to savolitinib, suggesting a reference basis for the treatment of similar cases with EML4-MET fusion in the future. Additional research is warranted to assess the biological significance of the EML4-MET fusion in NSCLC.

The benefit of high-dose melphalan followed by autologous hematopoietic stem cell transplantation (HDM-ASCT) for multiple myeloma (MM) patients with renal insufficiency (RI) is debated. A systematic review and meta-analysis were conducted to assess the safety and efficacy of HDM-ASCT in MM patients with RIs, and the findings were compared with real-world data. The study included 26 articles, 13 of which were pooled for meta-analysis. We compared three different types of MM patients with RI against MM patients with normal renal function (NRF). These patients were: MM patients with RI at the time of transplantation; MM patients with RI at the time of diagnosis; MM patients with RI at diagnosis but with NRF at transplantation. The meta-analysis indicated that MM patients with RIs conditioned with melphalan ≤ 140 mg/m2 followed by ASCT had transplant-related mortality rates comparable to those without RIs. The complete response rates post-ASCT were similar between MM patients with RIs and those with NRF. Although progression-free survival (PFS) was statistically similar between the groups, MM patients with RIs had significantly poorer overall survival (OS) than those with NRF. The real-world data supported these findings. With a reduced dose of melphalan, ASCT is safe and effective for MM patients with RI. MM patients with RI have similar complete response rates and PFS after ASCT compared to MM patients with NRF. The lower OS in MM patients with RI indicates the need for further research to improve OS in these patients.

Over the last decade, epidermal growth factor receptor (EGFR)-targeted therapies have transformed the treatment landscape for patients with advanced solid tumors. Despite these advances, resistance to anti-EGFR therapies is still a significant clinical challenge. While cell-autonomous mechanisms of resistance are well-documented, they do not fully elucidate the complexity of drug resistance. Cancer-associated fibroblasts (CAFs), key mediators within the tumor microenvironment (TME), have emerged as pivotal players in cancer progression and chemoresistance. Recent evidence implicates CAFs in resistance to anti-EGFR therapies, suggesting they may undermine treatment efficacy. This review synthesizes current data, highlighting the critical role of CAFs in resistance pathogenesis and summarizing recent therapeutic strategies targeting CAFs. We underscore the challenges and advocate for the exploration of CAFs as a potential dual-targeted approach.

AbstractObjectiveTQB3602 is a novel orally bioavailable proteasome inhibitor. This study is the first‐in‐human phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of TQB3602 in relapsed/refractory multiple myeloma (RRMM).MethodsThis is a multicenter phase I clinical trial consisting of the 3+3 dose‐escalation phase and dose expansion phase. Patients with MM who have received ≥2 prior antimyeloma therapies were enrolled. TQB3602 is administered at a dose of 0.5~7mg on days 1, 8, 15 in 28‐day cycle.ResultsTwenty‐five RRMM patients who relapsed or failed ≥2 lines of therapies were enrolled in the dose escalation phase. Two patients in the 7.0 mg dose group developed dose‐limiting toxicity events (one with grade 2 peripheral neuropathy [PN] complicated by pain and one with diarrhea and abdominal pain), leading to a maximum tolerated dose of 6.0 mg. Any‐grade adverse events (AEs) occurred in 24 (96.0%) patients, while grade ≥3 AEs occurred in 13 (52.0%). The most common grade ≥3 AEs was anemia (6, 24.0%). The incidence rate of PN was 16% with no grade ≥3 PN occurred. TQB3602 was rapidly absorbed, resulting in a time‐to‐plasma peak concentration of 0.8–1.5 h. The mean half‐life was approximately 82 h. The AUClast and Cmax were approximately 1.9 times higher on day 15 than on day 1. Among 22 response‐evaluable patients, 63.7% achieved stable disease or better.ConclusionsTQB3602 is well tolerated, with a favorable neurotoxicity profile, and has shown preliminary efficacy in patients with RRMM. The anticipated therapeutic dose was 6 mg and was adopted for an ongoing dose‐expansion phase.

The role of local ablative radiotherapy (stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS)) in the management of metastatic breast cancer (mBC) patients remains unclear. This study aimed to assess the efficacy of SBRT/SRS in oligometastatic and oligoprogressive breast cancer patients. Totally 80 mBC patients with oligometastatic disease (OMD) and 80 with oligoprogressive disease (OPD) to ≤5 metastatic lesions were retrospectively analyzed. The endpoint was overall survival and progression-free survival, and univariate and multivariate analyses were performed for survival analysis. Totally 160 mBC cases (80 OMD and 80 OPD cases) were analyzed, with a total of 291 treated metastases. In the study of OMD, we analyzed 30 cases with oligo-recurrence and 50 cases with sync-oligometastases. The median follow-up time was 46 months, and 1-, 2-, and 3-year OS rates for all patients were 89.8

BackgroundDriver mutations in tyrosine kinases, such as the anaplastic lymphoma kinase (ALK) mutation, are known to play a critical role in the pathogenesis of non-small cell lung cancer (NSCLC) but are rarely observed in large cell neuroendocrine carcinoma (LCNEC). Multiple primary malignancies (MPMs) refer to the occurrence of two or more distinct primary malignancies within the same or different organs and tissues in a single patient, either simultaneously or sequentially.Case PresentationWe reported a case of advanced LCNEC as a heterochronous double primary malignancy, following a prior breast cancer diagnosis in a 55-year-old woman. Ten years after achieving remission from breast cancer, the patient was diagnosed with LCNEC, presenting with multiple brain metastases (BMs) after undergoing surgery and adjuvant radiochemotherapy. She tested positive for the ALK fusion gene and received lorlatinib as an initial treatment. After 6 weeks, there was a significant reduction in the tumor, and the treatment impact was evaluated as a partial response. The treatment has been continued for over 25 months since the initiation of ALK Tyrosine kinase inhibitor (ALK-TKI) therapy.ConclusionThis case suggested that ALK-positive advanced LCNEC patients might benefit from first-line intervention with lorlatinib, particularly for managing brain metastases.

Background: Multiple myeloma (MM) is the second most common hematological malignancy without cure, and Chimeric Antigen Receptor T Cell (CAR-T) therapy has been shown great promising in MM. Unlike previous published studies mainly focusing on efficacy and safety, this study aims to summarize time points in the process of CAR-T therapy in MM and establish a standardized time-related CAR-T therapy platform to provide a reference for CAR-T treatment in MM.Methods: All the literatures were retrieved from PubMed, Web of Science, Embase, American Society of Hematology (ASH), American Society of Clinical Oncology (ASCO) and European Hematology Association (EHA). Relevant median detection time of efficacy and safety-related indicators of CAR-T therapy in MM were extracted from included literatures, and median values were applied to represent detection time points of indicators. Notably, the median values were not the certain and optimal detection time points, while the significance is that indicators could be detected more frequently around the median values to obtain the ideal results.Results: This review presented the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM according to the chronological order. For short-term effects on inflammation status within 1 month after CAR-T initiation, the median time points of cytokine release syndrome onset, immune effector cell associated neurotoxicity syndrome onset, neutrophils recovery and CAR-T expansion peak were 4.5, 8, 10 and 12 days, respectively. For medium-term effects on clinical response in MM beyond 1 month and up to 3 months following CAR-T infusion, the median time points of minimal residual disease negativity, the reduction of serum light chain to minimum, platelet recovery and the reduction of M protein to minimum were 30, 30, 44 and 90 days, respectively.Conclusions: This systematic review summarized the median detection time points of efficacy and safety-related indicators of CAR-T therapy in MM and constructed the time-related CAR-T therapy platform, providing an evidence-based standard for establishment of CAR-T treatment regimen in MM.

Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.

Although the development of novel drugs has significantly improved the survival of patients with multiple myeloma (MM) over the past decades,the lack of effective therapeutic options for relapsed and refractory MM results in poor prognosis.The chimeric antigen receptor (CAR) T-cell therapy has achieved considerable progress in relapsed and refractory MM.Nevertheless,this therapy still has limitations such as cytokine release syndrome,neurotoxicity,and off-target effects.Natural killer (NK) cells,as a critical component of the innate immune system,play an essential role in tumor immunosurveillance.Therefore,CAR-modified NK (CAR-NK) cells are put forward as a therapeutic option for MM.The available studies have suggested that multiple targets can be used as specific therapeutic targets for CAR-NK cell therapy and confirmed their antitumor effects in MM cell lines and animal models.This review summarizes the anti-tumor mechanisms,biological characteristics,and dysfunction of NK cells in the MM tumor microenvironment,as well as the basic and clinical research progress of CAR-NK cells in treating MM.

Thymoma combined with pure red cell aplasia (PRCA) and acquired amegakaryocytic thrombocytopenia (AAMT) has been rarely reported, often occurring in the initial stage of treatment and after chemotherapy or thymectomy, while PRCA and AAMT occurring after radiotherapy for thymoma has not been reported. The present study describes the case of a 42-year-old female patient with thymoma complicated by radiation-induced PRCA and AAMT after a rapid response to radiotherapy, who was in complete remission without recurrence after adjustment of initial symptomatic therapy to cyclosporine combined with prednisone. After 1 month, the patient underwent complete resection of mediastinal tumor. Next-generation sequencing revealed that the DNA damage repair pathway-related gene MSH3 was mutated, with p.A57P in abundance of 9.21%. To the best of our knowledge, the present study is the first to report that PRCA and AAMT secondary to thymoma after radiotherapy may be associated with increased sensitivity to radiotherapy caused by a mutation in the MSH3 gene.

Background: For multiple myeloma (MM), the proportions of patients reaching the subsequent line of therapy (LOT) decline gradually and real-world data describing the attrition rates of LOT in Chinese MM were limited. Herein, we investigated the attrition rates by subsequent LOTs and their relevant risk factors in MM patients in China.Methods: MM patients who had been hospitalized and received at least one LOT from January 2008 to August 2019 in West China Hospital Sichuan University were retrospectively recruited. Demographic and clinical characteristic data were obtained from the "HemaTank " Chinese Multiple Myeloma Database. The Cox proportional hazards regression model was applied to analyze the risk factors of frontline treatment attrition.Results: A total of 1,255 newly diagnosed MM were enrolled, with 573 (45.7%) patients receiving only one LOT and 682 (54.3%) patients receiving more than one LOT. Thalidomide with dexamethasone/prednisone was the most common frontline treatment before 2017, while bortezomib-based regimens constituted the majority of frontline treatment in 2017 and beyond. The attrition rates from the first to the fifth LOT exhibited a gradual upward trend (45.7%, 48.7%, 58.9% and 62.5%, respectively). Meanwhile, 54.3%, 27.9%, 11.5%, and 4.3% of all the enrolled MM patients received a second, third, fourth and fifth LOT. MM who underwent autologous stem cell transplantation (ASCT) showed lower attrition rates across all LOTs (range 12%-56.8%) than MM without ASCT (range 49.1%-64.5%). The multivariate Cox regression model revealed that ISS stage III (HR 2.07, p < .001), elevated LDH (HR 1.47, p = .006), and comorbidities such as amyloidosis (HR 1.63, p = 0 .01), hepatic disease (HR 1.36, p = .022), pulmonary disease (HR 1.38, p = .022), and cardiac disease (HR 1.62, p = .004) were independent risk factors for MM patients attritted from the frontline treatment.Conclusion: In this study, the attrition rates were generally high and increased gradually across all LOTs. Nearly half of MM patients received only one LOT, and higher tumor burden and more comorbidities may be associated with fewer subsequent LOTs. The high attrition rates highlight the importance of applying the most optimal frontline treatment regimen rather than salvaging subsequent LOTs.

Background: China is a highly endemic area for Hepatitis B virus (HBV) infection and HBV reactivation is an event of concern in treating patients with hematologic malignancy. However, there were very few reports regarding HBV reactivation in patients with multiple myeloma (MM) in China. Since the approval of novel agents, especially immunotherapy such as monoclonal antibody and chimeric antigen T cell immunotherapy, the risk of HBV reactivation has increased. Therefore, the study aimed to evaluate the HBV infection status in MM and explore the incidence and risk factors of HBV reactivation in MM patients in China. Methods: Newly diagnosed MM patients with available serologic assays for HBV infection were retrospectively enrolled between June 30, 2008 and December 30, 2022 in West China Hospital, Sichuan University. Demographic and clinical data were obtained from the “HemaTank” Chinese Multiple Myeloma Database (HCMMD). Meanwhile, patients diagnosed with Waldenstrom Macroglobulinemia (WM) at the same time were enrolled as the control group. HBV reactivation was defined as the occurrence of one of the following: ≥ 2 log increase in HBV-DNA levels from baseline level, detection of HBV-DNA with level > 100 IU/ml in a person with undetectable HBV DNA at baseline or HBsAg-negative becoming positive. The penalized maximum likelihood logistic regression for rare events was applied to identify independent risk factors related to HBV reactivation. Results: The study recruited 3040 MM patients with a median age of 62 (range 14~98) and 240 WM patients with a median age of 63 (range 25~92). The HBsAg-positive rates were similar between MM and WM (9.4% vs 10.8%, P=0.49), but both the HBcAb-positive rates and HBeAb-positive rates in WM were significantly higher than MM (76.3% vs 60.7%, P<0.001; 37.5% vs 25.1%, P<0.001). The analysis of co-expression of HBV markers shows that the prevalence of HBsAg-/Anti-HBs+/anti-HBC- in MM was significantly higher than WM (16.7% vs 8.3%, P<0.001) and HBsAg-/Anti-HBs-/anti-HBC+ in MM was significantly lower than WM (18.3% vs 27.1%, P<0.001). However, he prevalence of HBsAg+/ HBeAg+/anti-HBC+ and HBsAg+/ anti-HBeAb+/anti-HBC+ were similar between MM and WM (0.5% vs 1.3%, P=0.158; 8.6% vs 8.8%, P=0.503). The baseline characteristics of HBsAg-positive MM and HBsAg-negative MM were summarized in Table 1. The rates of HBsAg-positive MM were significantly increased in young male patients (P<0.05). The level of ALT and AST, and the incidence of HBV reactivation, liver cirrhosis and pulmonary disease were significantly higher in HBsAg-positive MM than in HBsAg-negative MM (P<0.05). Of the 2147 MM patients who have received at least one line of chemotherapy (Table 1), 924 (43%) MM patients received bortezomib-containing or lenalidomide-containing regimens as the frontline therapy, while only 21 (1.0%) received a daratumumab-containing regimen as the frontline therapy. During hospital-documented follow-up visits, 26 (1.21%) MM patients have experienced HBV reactivation. According to the multivariate analysis of risk factors for HBV reactivation in MM, liver cirrhosis (OR 8.63, 95%CI 2.95-25.24, P<0.001), autologous stem cell transplantation (OR 6.03, 95%CI 2.47-14.72, P<0.001) and HBsAg-positive (OR 14.45, 95%CI 6.50-32.14, P<0.001) were independent risk factors associated with high prevalence of HBV reactivation. The ROC curve of the model integrating the three factors is shown in Figure 1, and the AUC was 0.8584. Conclusions: Among Chinese MM patients with multiple myeloma, a high proportion of MM patients presented with resolved hepatitis B virus infection, whereas HBV reactivation was pretty rare. However, long-term HBV DNA levels monitoring is still needed for MM patients at high risk for HBV reactivation.

Multiple myeloma (MM) is a heterogeneous disease that remains incurable with significant interpatient variability in outcomes.Regulatory B cells (Bregs) were observed to be involved into specific defects in MM.Here, we provide our risk-adapted approach to newly diagnosed MM (NDMM), combining with the fundamental dysfunction of Bregs.We reported one hundred consecutive patients with NDMM from South-Western China, primarily treated with bortezomib plus dexamethasone with or without a 3 rd agent, were enrolled from 2017.Bone marrow aspirates were obtained and flow cytometry (FCM) was used to quantify the percentage of Bregs from the bone marrow.The correlation between Bregs and clinical characters were further analyzed.This study found using bortezomib plus dexamethasone as backbone showed promising efficacy with acceptable tolerability in NDMM.The relatively compromised progression free survival (PFS) points to the essential synergy of bortezomib and lenalidomide here.This study also found that altered proportions of Bregs were closely correlated with treatment efficacy and prognosis in MM.Further understanding of Bregs biology might provide new opportunities to develop immunotherapy, which could prove beneficial in treating MM.

Background Characterization of the tumor microenvironment is helpful to understand the tumor immune environment of lung cancer and help predict the prognosis. Methods First, immune subtypes were identified by consensus subtype among lung squamous carcinoma (LUSC) patients. Immune cell infiltration was evaluated by CIBERSORT and ESTIMATE analyses. Then, based on differentially expressed genes (DEGs) identified, a risk score model was constructed. Finally, gene FPR1 was validated by using YTMLC-90. Findings LUSC samples were divided into four heterogeneous immune subtypes, with significantly different prognoses with subtype 4 having the poorest overall survival (OS). The immune infiltration score showed that subtype 4 was characterized as immune enriched and fibrotic, while subtype 3 was tumor enriched. DEG analysis showed that upregulated genes in subtype 4 were enriched of neutrophil and exhausted T cell-related biological processes. Based on a univariate Cox regression model, prognostic 7 immune-related genes were combined to construct a risk score model and able to predict OS rates in the validation datasets. Wound healing and transwell assay were conducted to evaluate the invasion property after activating the gene FPR1. Interpretation The analysis of tumor immune microenvironments among LUSC subtypes may provide new insights into the strategy of immunotherapy.