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Introduction: Teclistamab, the first approved B‐cell maturation antigen‐directed bispecific antibody for treatment of triple‐class exposed relapsed/refractory multiple myeloma, demonstrated deep, durable responses with a manageable safety profile in the pivotal MajesTEC‐1 cohort (NCT03145181/NCT04557098). Efficacy, safety, and pharmacokinetics from the MajesTEC‐1 China cohort are reported. Methods: Patients received teclistamab 1.5 mg/kg subcutaneously weekly after step‐up dosing; patients could switch to less frequent dosing with continued response. Results: In the China cohort (N = 26; median age, 66 years; median prior lines of therapy, 5) 15‐month median follow‐up, overall response rates, very good partial response or better, and complete response or better (≥CR) were 76.9%, 76.9%, and 57.7%, respectively. Median time to first response and ≥CR were 1.4 and 6.3 months, respectively; among patients with ≥CR and have available MRD samples, MRD negativity was achieved in 14/15 (93.3%) patients. Median duration of response, progression‐free survival, and overall survival were not reached; 12‐month duration of response, progression‐free survival, and overall survival rates were 78.5%, 68.0%, and 83.5%, respectively. The safety profile was consistent with the pivotal cohort. Although infections occurred in 96.2% of patients, incidence decreased over time with six patients experiencing infections for >12 to 18 months. There were no discontinuations because of adverse events and no dose reductions. Ten patients switched to less frequent dosing. Teclistamab serum concentrations were consistent with the pivotal cohort, with a slightly lower mean pharmacokinetics profile. Conclusions: Teclistamab demonstrated efficacy and safety profiles in the China cohort consistent with the pivotal cohort, supporting teclistamab as a promising treatment option for triple‐class exposed relapsed/refractory multiple myeloma in China. In the MajesTEC‐1 China cohort, teclistamab showed deep and durable responses, a manageable safety profile, and pharmacokinetics consistent with the pivotal recommended phase 2 dose cohort. These findings support teclistamab for heavily pretreated patients with relapsed/refractory multiple myeloma in China. [ABSTRACT FROM AUTHOR]

Background: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non‐Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient‐specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. Methods: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan‐Meier method coupled with the log‐rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. Results: The median age of the cohort was 60.0 years with a male‐to‐female ratio of 3.36:1. Five‐year progression‐free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High‐intermediate/high‐risk group according to MIPI‐c, without high‐dose cytarabine, lack of Auto‐SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high‐intermediate/high risk group according to MIPI‐c, without high‐dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. Conclusions: First‐line high dose cytarabine exposure, auto‐SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients. [ABSTRACT FROM AUTHOR]

Background: The use of proteasome inhibitors (PIs), new immune modulators (IMiDs), and other new drugs, as well as high‐dose chemotherapy combined with autologous stem cell transplantation has considerably improved the survival of young patients with multiple myeloma (MM). However, the improvement in survival among elderly patients remains insufficient. Optimal treatment recommendation models for elderly patients with MM have not been developed especially there are quite few study in the real world. Methods: We retrospectively analyzed the treatment patterns and outcomes of 328 Chinese patients (≥65 years) with MM in a real‐world setting. Patients were divided into three groups according to induction regimens. Results: The median age of the cohort was 70 (65–86) years. The patients were divided into group 1 (PIs based regimens, n = 218), group 2 (IMiDs based regimens, n = 48) and group 3 (PIs + IMiDs, n = 62). Induction regimens in group 3 produced higher overall response rate than group 1 and 2 (85.42% vs. 71.08% vs. 66.67%, p = 0.016). The median follow‐up of the cohort was 30 (interquartile range [IQR] 18–36) months. For the entire cohort median progression‐free survival (PFS) was 26 (IQR 12.00–42.89) months and overall survival (OS) was 60 (IQR 40.00–67.20) months. The PFS were not significantly different among the three groups (28 months vs. 18 months vs. 26 months, p = 0.182). So were the OS (60 months vs. 59 months vs. not reached, p = 0.067). Multivariate analysis revealed that age >70 year, frailty status (Geriatric vulnerability score), induction efficacy < partial remission, and no maintenance treatment were independent poor prognostic factors for OS. Conclusion: Front‐line induction regimens combining PIs and IMiDs developed more deep response than single PI or IMiD based regimens. Maintenance treatment can further improve the clinical outcome in elderly MM patients in real‐world setting. [ABSTRACT FROM AUTHOR]

The medium-sized Daping gold deposit is located in the middle Xuefeng Mountain area of Southern China with gold ores hosted in sericite phyllite, sericitolite, and mylonite. The auriferous quartz-carbonate-sulfide veins and adjacent alteration rocks are structurally controlled within the NE (northeast) shear zone with NE, NNE (north-east-east), and NW (northwest) trending at high inclination angles. The petrogeochemistry analysis results show that the gold ores are characterized by high content values of SiO2, S, and As and low content values of Al2O3 and Na2O and display strong enrichment of LREE with δEu values ranging from 0.54 to 0.75. Four stages of mineralization/alteration were identified: the first stage has mineral assemblages of quartz+pyrite+arsenopyrite±carbonate minerals, the second stage has mineral assemblages of quartz+polymetallic sulfide minerals (pyrite, arsenopyrite, chalcocite, galena, chalcopyrite, tetrahedrite)±chlorite±carbonate minerals, the third stage has mineral assemblages of quartz and carbonate minerals, and the supergene stage is characterized by limonite±patina which were formed by the oxidation of metal sulfides. Among them, the first stage and the second stage are the main gold mineralization stages. The ore-forming fluid inclusions in quartz are mainly composed of liquid phase (H2O) and gas phase (H2O and CO2), and based on the microthermometric analysis, the first metallogenic stage and second metallogenic stage yielded average homogenization temperature of 184.5 and 255.8°C and average salinity of 7.64 wt.% NaCl eqv. and 11.35 wt.% NaCl eqv., respectively. Thus, the ore-forming fluids belong to H2O-CO2-NaCl, medium-low temperature, and medium-low salinity fluid. The δ D H 2 O and δ 18 O H 2 O values of auriferous quartz are from -51‰ to 62‰ and from -1.44‰ to 5.42‰, respectively, indicating that the ore-forming fluids may belong to mixing fluids of the magmatic fluid and meteoric hydrothermal fluid. The values of δ34S of metal sulfides range from -0.94‰ to 1.98‰ (-0.131‰ in average), implying that sulfur may source from the concealed granite and/or basement metamorphic strata. The Daping gold deposit formed in the Indosinian period under the tectonic environment of compression between the Cathaysian plate and Yangtze plate and may belong to orogenic gold deposits. [ABSTRACT FROM AUTHOR]

Relapsed and refractory (R/R) idiopathic Multicentric Castleman disease (iMCD) is a clinical challenge with few treatment options. In this first multicenter, prospective trial which implemented the recently published CDCN response criteria, we evaluated the efficacy and safety profiles of bortezomib-cyclophosphamide-dexamethasone (BCD) regimen in 24 R/R iMCD patients. By 6 months, 15 patients (62.5%) achieved overall treatment responses; four patients (16.7%) had stable disease and five patients (20.8%) suffered from progression of disease. Even when considering all patients, there were significant (p <.05) improvements in median symptom score, hemoglobin, platelet count, C-reactive protein (CRP) erythrocyte sedimentation rate (ESR), IL-6, albumin, and immunoglobin G (IgG) after treatment. The regimen was well tolerated without grade 3 or higher adverse events. Estimated 1-year progression-free survival (PFS) and overall survival (OS) were 79% and 92%, respectively. BCD regimen is an effective and safe treatment option for R/R iMCD patients. This trial was registered at as # ChiCTR1800019342. [ABSTRACT FROM AUTHOR]

Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis.Methods: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model.Results: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89).Conclusions: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372. [ABSTRACT FROM AUTHOR]

To investigate the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on chemokine receptors and explore the potential mechanism of rhG-CSF inducing immune tolerance, ninety-seven donor and recipient pairs undergoing family-donor allogeneic hematopoietic stem cell transplantation were studied. The results indicated that different donors showed great disparities in expression changes after mobilization. Multivariate analysis revealed that both HLA mismatching and CCR7 downregulation on donors' CD4 + T cells after mobilization were independent risk factors for acute graft-versus-host disease (GVHD). In contrast, CCR5 downregulation on CD4 + T cells was associated with reduced incidence of acute GVHD. In conclusion, rhG-CSF mobilization could lead to differential regulation of chemokine receptors expression on T cell subsets in different donors. Downregulation of CCR5 and upregulation of CCR7 expression on donor CD4 + T cells might protect recipients from acute GVHD. This finding may provide a promising new strategy for the prevention and treatment of acute GVHD. [ABSTRACT FROM AUTHOR]

• Light chain cast nephropathy (LCCN) may exhibit a crystalline appearance. • Crystalline LCCN patients usually present with acute kidney injury. • The offending light chain of crystalline LCCN was mainly the λ isotype. • Crystalline LCCN patients had higher early mortality than ordinary LCCN patients. Light chain cast nephropathy (LCCN) is the most common kidney lesion in multiple myeloma patients. LCCN may exhibit a crystalline appearance. The frequency and clinical significance of crystalline LCCN are not well understood. Here, we report the first retrospective study of crystalline LCCN. Twenty-six patients with LCCN were enrolled. We studied the clinicopathological features and outcomes of LCCN patients and compared ordinary LCCN patients (n = 18) with crystalline LCCN patients (n = 8). Crystalline LCCN was not rare (8/26, 30.8%) in our study. The median age of LCCN patients was 57.5 (range, 41–75) years. No patients presented with nephrotic syndrome. No significant differences in clinical features were observed between the two groups. All crystalline LCCN patients suffered from advanced multiple myeloma and acute kidney injury. There was a dominance of the λ isotype (7/8, 87.5%) in patients with crystalline LCCN. Patients with ordinary LCCN had significantly higher scores of tubular atrophy and acute tubular injury than those with crystalline LCCN. The crystalline casts of 5 crystalline LCCN patients stained negative with antihuman Tamm-Horsfall glycoprotein. There were no significant differences in the median overall survival between the crystalline LCCN group and the ordinary LCCN group (6.0 months vs. 35.0 months, p = 0.173). However, crystalline LCCN patients had higher early mortality than ordinary LCCN patients (50.0% vs 11.1%, p = 0.03). Crystalline LCCN patients had higher early mortality than ordinary LCCN patients. Thus, for patients with LCCN, crystalline appearance should be screened carefully. [ABSTRACT FROM AUTHOR]

• We report a novel recombinant human astrovirus, Y/1−CHN, identified in two immunocompromised patients following allo-HSCT in this study. It is showed that the virus caused prolonged infection involving diversified quasispecies in the hospitalized immunocompromised patients, indicating such patients are a reservoir for new astrovirus variants, their excreta should be monitored even after discharge from hospital. Human astroviruses (HAstVs) were first identified in 1975 and can be classified into three clades: classic HAstVs (HAstV 1–8), MLB (MLB1−3) and VA (VA1−5), with MLB and VA were newly identified. Recombination and a high mutation rate make HAstV as one of the rapidly evolving infectious agents. This study reported a novel identified recombinant human astrovirus (Y/1−CHN) and its long existence in two immunocompromised patients with diarrhea following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The identified Yu/1−CHN genome contains 6801 base pairs encoding three open reading frames, with ORF1a best hit to the HAstV1 (Pune strain, 97 % nucleotide identity), while ORF1b and ORF2 best hit to HAstV-5 (DL30 strain, 99 % nucleotide identity). Possible recombination breakpoint was predicted to be located in the boundary of ORF1a and ORF1b. Different quasispecies were found in the host, and the dN/dS ratios of the S and P domains were determined to be 1.189 and 1.444, respectively, suggesting a positive selection existed. Fecal samples collected in different clinical phases from the two patients were all positive for Yu/1−CHN, suggesting a long existence of the virus in the host. It was indicated that immunocompromised patients may a reservoir for astrovirus, their excreta should be monitored even after discharge from hospital. [ABSTRACT FROM AUTHOR]