Introduction Chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough in the treatment of relapsed or refractory (R/R) multiple myeloma (MM), however, severe cytokine release syndrome and neurotoxicity may compromise outcomes. A well-tolerated bridging therapy that controls disease without additional toxicities could improve the safety and efficacy of subsequent CAR-T infusion. Aponermin, a novel circularly permuted TRAIL ligand, induces selective apoptosis in malignant plasma cells through death receptors DR4 and DR5 (Dhillon S, Drugs, 2024; Xia Z, Leng Y, Fang B, BMC Cancer, 2023). The safety and efficacy of aponermin-based regimens as bridging therapy before CAR-T treatment remain to be explored. Methods We performed a retrospective, three-centre cohort study of consecutive RRMM patients who received aponermin-based chemotherapy after leukapheresis and before lymphodepletion (fludarabine 30 mg/m²/day and cyclophosphamide 300 mg/m²/day × 3 days) followed by a single BCMA CAR-T infusion. Safety and efficacy were assessed from the start of bridging therapy until 30 days after CAR-T administration. Results Twenty-eight patients with R/R MM were enrolled. All had received a median of four prior lines of therapy (range 3–7). Among them, 27 patients presented with extramedullary disease. All patients were refractory to proteasome inhibitors, immunomodulatory drugs, and CD38 monoclonal antibodies. Of the 28 patients, 23 received one cycle of bridging therapy, 3 received two cycles, and 1 patient received three cycles. After aponermin-based bridging therapy, the overall response rate (ORR) was 41.7% (7/28), including a complete response (CR) in 7.1% (2/28) patients and a partial response (PR) in 17.9% (5/28) patients. Stable disease (SD) was observed in 17 (60.7%) patients, and 2 (7.1%) patients experienced disease progression after bridging therapy. The safety profile of bridging therapy was favorable, with only one case of hypersensitivity reaction and two cases of elevated transaminases. Notably, six patients with stable disease after bridging therapy experienced significant platelet elevation after bridging therapy, potentially reducing bleeding risk during subsequent CAR-T cell treatment. Among 23 evaluable patients after CAR-T cell treatment, the ORR was 95.7 % (sCR 4.3 %, CR 17.4 %, PR 52.2 %). The median progression-free survival (PFS) was 6.43 months. Conclusion: Aponermin-based bridging therapy is well tolerated, does not exacerbate organ dysfunction or marrow suppression, and provides significant disease control or platelet recovery. These findings support prospective evaluation of aponermin-based regimens as an effective bridge to BCMA CAR-T therapy in R/R MM.

Acute myeloid leukemia (AML)'s treatment and remission remains unsatisfactory. A prognostic risk-scoring model containing seven signature genes (POU3F1, RPGR, PTP4A3, SOCS1, FAM83G, GREB1 and COL2A1), was developed by LASSO-Cox regression analysis. In the training set, the test group, area under the curve values of 1, 3, and 5 years were 0.876, 0.877, 0.937, and 0.974, 0.878, 0.976 respectively, which indicates a good predictive efficacy. In the two external GEO (GSE71014 and GSE6891) datasets, area under the curve values of 1, 3, 5 years were 0.847, 0.857, 0.822, and 0.830, 0.863, 0.891 respectively. Our seven signature genes containing risk-scoring model performed excellently in evaluating the OS of AML patients.

Background:In the absence of a human leukocyte antigen (HLA)-matched donor, intensive immunosuppressive therapy (IST) combined with unrelated cord blood (IIST-UCB) a salvage treatment option for patients with severe aplastic anemia (SAA) who had failed IST. With advancements in transplantation technology, outcomes of IIST-UCB have improved considerably in recent years. Here, we will focus on the differential effects of IIST-UCB on patient survival and GVHD risk and evaluate its therapeutic efficacy between SAA and VSAA patients. Methods:Between August 2004 and May 2024, 115 SAA patients were screened at enrollment. The overall survival (OS) rates and failure-free survival (FFS) rates were evaluated and compared using Kaplan-Meier curves and log-rank tests. Cumulative incidences of cytomegalovirus (CMV), hematopoietic recovery, and Epstein-Barr virus (EBV) were estimated using a competing risk regression model. Results:The median age was 16 years (range, 2-74). At 6 months, 27 patients (27%) achieved complete response (CR), and 44 patients (44%) achieved partial response (PR). The median period to neutrophil engraftment was 25 days, and to platelet engraftment was 44 days. The 250-day cumulative incidence of hemoglobin recovery was 87.8% (95% CI, 77.7%-93.6%). The 100-day cumulative incidence of neutrophil engraftment was 88.5% (95%CI, 80.6%-93.3%). The 400-day cumulative incidences of platelet engraftment was 86.7% (95%CI, 77.5%-92.4%). The 5-year overall survival was 86.1% ± 6.66%, and the 5-year failure-free survival was 72% ± 8.62% in the cohort. Transplantation-related mortality was 12.5% (95% CI, 7.2%-19.4%). No acute or chronic graft-versus-host disease (GVHD) was observed during the entire period. The cumulative incidences of CMV and EBV were 7.18% (95% CI, 3.34%-13%) and 16.8 (95% CI, 10.6%-24.3%), respectively. The majority of patients exhibited microchimerism and maintained hematopoiesis over the long term. Patients with SAA who received UCB treatment showed significantly higher hematopoietic reconstitution efficiency (P = 0.004, P = 0.001, P = 0.001) and overall survival compared with the VSAA group (P = 0.028). Conclusion:These data support IIST-UCB as an alternative therapeutic approach for patients with SAA.

Background: In China, the utilization rate of ASCT as front-line therapy is merely 10%. Many transplant-eligible (TE) patients decline ASCT for various subjective and objective reasons. Recent studies, such as GRIFFIN (D-VRd) and CASSIOPEIA (D-VTd), have shown promising results in TE-NDMM patients receiving ASCT as initial therapy. These findings have prompted us to investigate the potential efficacy of D-VRd in standard-risk patients. This interim analysis presents the first open-label, single-arm study evaluating the efficacy and safety of D-VRd in TE-NDMM patients with standard risk who declined ASCT in China (NCT 05088330). Methods: We enrolled NDMM patients, as per IMWG criteria, who were transplant-eligible but voluntarily declined ASCT. Patients with t(4;14), Del(17p), t(14;16), or R-ISS stage III were excluded. The D-VRd regimen consisted of: Daratumumab: 16 mg/kg I.V. weekly for 2 cycles, then every 3 weeks for 6 more cycles, bortezomib: 1.3 mg/m2 SC, Days 1, 4, 8, 11 for 8 cycles, lenalidomide: 25 mg P.O., Days 1-14 for 8 cycles, dexamethasone: 20 mg P.O., Days 1, 2, 4, 5, 8, 9, 11, 12 for 8 cycles. Patients then received Daratumumab 16mg/kg I.V. monthly for 1 year as maintenance therapy. The primary endpoint was NGS MRD negativity at 10-5 after 8 cycles of D-VRd. Secondary objectives included ORR, sCR, ≥CR, ≥VGPR, AEs, TTR, and DOR. Stem cell collection was recommended after 4 cycles of D-VRd. Result: As of June 30, 2024, 46 patients were enrolled in the study. The median age was 62 years (range: 38-74), with 23 (50.0%) male patients. Cytogenetic analysis revealed 27 (58.7%) patients with 1q gain (3 copies) and 4 (8.7%) patients with t(11;14). Additionally, 8 (17.4%) patients presented with renal insufficiency, and 6 (13%) had extramedullary disease (EMD). The overall response rate (ORR) was 97.4%, with 89.7% of patients achieving VGPR or better. Notably, 64.1% of patients attained CR or sCR. The median duration of treatment was 10 months (range: 1-21). The median number of treatment cycles was 9. Post-induction stem cell collection and storage was successful underwent in 19 (41.3%) patients. With a median follow-up of 12 months (range: 1-23), 72.7% (16/22) of patients achieved NGS MRD negativity after 8 cycles. Subgroup analysis comparing patients with 1q gain versus those without showed ORR, CR+sCR, and 1-year progression-free survival (PFS) rates of 95.8%, 58.3%, and 88.2% versus 100%, 73.3%, and 100%, respectively (p>0.01). Treatment-related adverse events (TRAEs) primarily consisted of hematological toxicities, occurring in all 46 (100%) patients. These included thrombocytopenia in 80.4% (n=37; 22 Grade 1-2, 15 Grade 3-4), lymphopenia in 58.7% (n=27; 17 Grade 1-2, 10 Grade 3-4), and neutropenia in 43.4% (n=20; 9 Grade 1-2, 11 Grade 3-4) of patients. Other adverse events (AEs) included ALT/AST elevation in 43.4% (n=20; 19 Grade 1-2, 1 Grade 3-4) and peripheral neuropathy (PN) in 45.7% (n=21; 12 Grade 1-2, 9 Grade 3-4) of patients. Infusion-related reactions were reported in 23.9% of patients (n=11, all Grade 1-2). Pneumonia occurred in 13.0% of patients (n=6, all Grade 3), with all cases resolving. One patient discontinued lenalidomide due to pulmonary embolism. Conclusion: Interim analysis of this study demonstrates that D-VRd treatment elicits rapid and deep responses in Chinese standard-risk, transplant-eligible newly diagnosed multiple myeloma (SR TE-NDMM) patients who declined ASCT, including those with 1q gain. The high rate of NGS MRD negativity (72.7%) before maintenance therapy underscores the regimen's efficacy. While hematological toxicities were the most common adverse events, they were generally manageable after the initial two cycles, indicating an acceptable safety profile. These promising results warrant further investigation to confirm the long-term efficacy and safety of D-VRd in this patient population.

The disease course of most patients with multiple myeloma (MM) is still characterized by a repeating pattern of periods of remission and relapse as their cycle. Relapse is attributed primarily to minimal residual disease (MRD). At any stage in the disease evolution, achievement of MRD negativity will predict for a better outcome. Despite its incorporation into the IMWG response criteria, what has not been clearly defined, however, is what to do when MRD positivity beyond a threshold level is detected, particularly when MRD levels are positive but overt relapse is not yet recognized. Daratumumab (DARA) targeting CD38 as an immunity therapy holds great promise. We referred to the pharmacokinetic data of smoldering myeloma from CENTAURUS study, and used the frequency of 16mg/kg DARA once every 4 weeks for early intervention in MM patients with persistent/recurrent MRD. We hypothesized that this therapy could be used to target and eliminate MRD to ultimately prolong progression-free survival in MM. A total of 23 patients were included in this study between January 2022 and December 2022. All participants were DARA-naïve and had achieved partial remission (PR) and above effects after first-line therapy including bortezomib and lenalidomide. DARA treatment after enrollment was given until clinical overt disease progression (PD) or unacceptable toxicity. We used next-generation flow assay (10-5) for subsequent regular BM aspirate MRD assessment. Among the 13 persistent MRD patients, all have achieved varying degrees of remission (CR/sCR: 8 cases (61.5%), VGPR: 4 cases (30.8%), and PR: 1 case (7.7%)). According to the IMWG criteria, 5 cases (50%) were accompanied by an increase in M protein, but had not yet reached the level of progression/biochemical relapse among the 10 MRD recurrent patients. For the perspective of response rate, 78.3% (18/23) patients achieved MRD negativity. In the persistent and recurrent MRD groups, the MRD conversion rates was 84.6% (11/13) and 70% (7/10), respectively (P>0.05). According to cytogenetic grouping, the conversion rate was 90.9% (10/11) and 66.7% (8/12) in the standard-risk and high-risk group, respectively(P>0.05). There was 1 case of standard-risk, 2 cases of double-hit and 2 cases of triple-hit among the 5 remaining positive patients. In the DARA monotherapy group and the DARA combining previous treatment agents group, the MRD conversion rate was 70% (7/10) and 84.6% (11/13), respectively (P>0.05). There was no statistically significant difference in the MRD conversion rate, regardless of intervention methods, MRD status or risk stratification. For the duration of negative MRD, until July 15, 2023, with a median follow-up of 12.3m [7.3-18.1m], the median duration of negative MRD in 18 reactive patients with negative MRD did not reach, superior to previous reports without additional intervention. In the persistent and recurrent MRD group, the percentage of MRD negativity lasting>12m is 81.8%(9/11) and 100%(7/7), respectively(P>0.05). Among the 2 patients who had once turned negative, progression occurred at the 9th and 12th month after DARA intervene, respectively. The percentage of MRD negativity lasting>12m is 100%（10/10）and 75%(6/8) in the standard-risk and high-risk group respectively(P>0.05). During the follow-up period, all the 4 patients who ultimately experienced PD were double hit high-risk MM, and there were no cases of PD in the standard-risk group. According to the NCI-CTCAE version 5.0, the rate of adverse events was low, similar to CASSIOPEIA trial. There were 2 cases of infusion reactions grade 1 during the first infusion. DARA dose delay occurred in 2 patients (1 due to severe COVID-19 pneumonia, and 1 due to hepatitis B virus activation). The most common adverse reaction was decreased immunoglobulin levels in 82.6% (19/23) cases. The median IgG level was monitored at 4.7 (3.6-10.2) g/L with 13% (3/23) IgG≤4g/L. The forthcoming results from MRD driven therapy trials are highly anticipated.

Background: Next-generation sequencing(NGS) assessment of minimal residual disease (MRD) at a sensitivity of 10−5 in multiple myeloma (MM) treatment response has just established in China recent years. MRD is one of the most powerful prognostic factors for progression-free survival and overall survival. It is adopted for evaluating therapy efficacy, tracking disease progression and making decision in MM trials. This retrospective study aims to investigate the role of MRD measured sequentially by the NGS in a real-world study. Methods:164 newly diagnosed multiple myeloma patients who received 4 cycles of VRD prior to ASCT or tandem ASCT with 2 more VRD consolidations at the first affiliated hospital of Soochow University from August 2019 to August 2023 were enrolled in this NGS MRD study and retrospectively analyzed. The 3 time points of MRD evaluation were after induction, post-transplantation and consolidation and before maintenance. To evaluate whether factors other than MRD status could affect patient prognosis, we used a Cox proportional hazard model including MRD status ,age, β2-MG, LDH, Creatinine clearance rate（Ccr）,extramedullary disease, R-ISS stage, and high-risk cytogenetics including del(17p), t(4,14), t(14,16), t(14,20), 1q21 gain/amp to explore their effects on OS and PFS. Results: The median age of patients at diagnosis was 58.5 (52-63) years. 12.8% patients were R-ISS III, 33% patients had high-risk cytogenetics. After induction, ORR was 91.8%, with 42.9% CR or better,37.8% VGPR,11.1% PR, 19.5% MRD negativity. After transplantation, ORR was 98.2%, with 59.6% CR or better, 30.5% VGPR, 8.1% PR, 44.5% MRD negativity. 76.3% patients with VGPR+ achieved MRD negativity. The proportion of MRD negative in CR patients increased significantly from induction to post-transplant (28 % vs 50%, p<0.003). With a median of follow-up of 29.3 months, 3-y PFS rate of patients achieving MRD - comparing to patients with MRD+ after induction was 100% vs 57.6% (p=0.014, HR=0.29, 95%CI 0.11-0.78). 3-y PFS rate was 79.9% vs 56.9%(p =0 .032, HR=0.43, 95%CI 0.20-0.93 ) for patients with MRD - versus MRD+ after transplantation. For Patients with MRD - vs MRD+ before maintenance , the respective 3-y PFS rate was 77.8% vs 51.3 % (p=0.046, HR=0.24, 95%CI 0.06-0.98). Three-year PFS rate was only 50.7% in patients with both MRD + after induction and transplantation. Median PFS was 37.3 months and only 23.4% patients are high cytogenetic risk. The time to progression was further divided into early-stage （<=18m,n=11）and late-stage progression(>=18m,n=16). There was a statistically significant difference in MRD + and cytogenetic risk between the two groups (91.9% vs 66.7%, 42.8% vs 18.1%, p=0.044). We found that the following factors negatively affected PFS in the univariate Cox model: MRD consecutive positive (p=0.0002),MRD status changing from negative to positive(p=0.007), Ccr<90 ml/min(p=0.035), extramedullary disease(p=0.046), R-ISS stage III (p=0.021)and high-risk cytogenetics(p<0.001). But MRD negative after induction (HR=0.13, 95%CI0.02-0.97, p=0.045) and transplantation (HR=0.34, 95%CI0.14-0.87, p=0.039) was associated with prolonged PFS. MRD consecutive positive (p=0.0043),MRD status changing from negative to positive (p=0.024) and high-risk cytogenetics (p=0.012)also had significant adverse impacts on OS. In the multivariate analysis, MRD consecutive positive, MRD status changing from negative to positive and high-risk cytogenetics were significantly associated with an inferior PFS, whereas only high-risk cytogenetics predicted a worse OS. Conclusion: This study demonstrates that patients achieved NGS MRD negativity before transplantation was associated with a prolonged PFS. But median PFS was only 37.3 months for those patients had sustained MRD positivity before and after transplantation regardless of cytogenetic abnormalities. High risk cytogenetics and MRD positive after transplantation resulted in earlier progression. These patients may need more aggressive intervention according to MRD monitoring.

Purpose: To evaluate the comparative efficacy of triple combination therapies of cyclophosphamide/dexamethasone containing either bortezomib or rituximab in treatment-naïve patients diagnosed with lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia, LPL/WM). Methods: Symptomatic, untreated patients with LPL/WM diagnosed in the First Affiliated Hospital of Soochow University were enrolled in this study and divided into two groups (BCD and RCD). Group BCD consisted of 16 patients administered bortezomib/cyclophosphamide/dexamethasone, while group RCD (15 patients) received rituximab/cyclophosphamide/dexamethasone. The efficacy of the two therapies and the Kaplan-Meier survival curve of the groups were evaluated. Results: With regard to overall response rate (ORR) and minimal response rate (MRR), there was no statistically significant difference between the 2 groups (100 vs 86.6 %, p = 0.226, and 81.25 vs 60.0 %, p = 0.252, respectively). The median time to minimal response (MR) in the BCD group was 1.3 months, which was shorter compared with that of RCD group (3.5 months, p = 0.026). Treatment-related toxicities (grade>2) were leukopenia, neutropenia, hypohepatia and pneumonia. With a median study follow-up of 27 months, disease in 18 patients (8 vs 10) progressed while 4 patients died (all in RCD group). The estimated median progression free survival (PFS) was 43 and 35 months in groups BCD and RCD, respectively, but the overall survival (OS) rate in 25 months significantly differed between the 2 groups (100 % vs 66.1 %，p = 0.033). Conclusion: The two regimens are active, produced responses and are safe as primary therapies for patients with LPL/WM. However, the response median time was much shorter in group BCD patients, and thus might have better survival benefits.

Background Autologous hematopoietic stem cell transplantation (ASCT) has always been considered as the standard choice for newly diagnosed multiple myeloma (NDMM) patients less than 65 years old, or even older. At present, how to define the patients who is suitable for transplantation is still controversial in clinic in China. Rate of utility of ASCT in front line was as low as 10%. The screening of transplant patients mainly depends on the evaluation of the general condition of patients, the wishes of patients and their families, and the evaluation of organ function by physical examination. In this way, it is particularly difficult for doctors in non-transplant medical units to recommend stem cell transplantation for patients. Based on “HemaTank” Chinese multiple myeloma database(HCMMD), a retrospective study of construction of special disease cohort and prognostic model for multiple myeloma were conducted to explore the posibilities of utility of IMWG/ECOG frailty score to select transplantation candidate, and the prognostic significance of frailty score in all MM patients. Methods In this study, 322 NDMM in the first affiliated Hospital of Soochow University from August 2018 to October 2022 were analyzed retrospectively. All patients were valuated with IMWG/ECOG frailty score before each cycle of treatment, which included age, the ECOG score, and the Charlson Comorbidity Index. Patients with IMWG frailty score≥2 were defined as frail, with score <2 were unfrail. Transplant patients received 4 courses of induction of VRd regimen followed by ASCT, and 2 courses of VRD consolidation after transplantation. Non-transplant patients received 8 courses of induction with VRD regimen. Standard risk patients received lenalidomide as maintenance therapy until PD. High risk patients received V+R as maintenance treatment until PD. Results The median age of 322 patients was 58(29-79). 178(55.3%) patients were male. 170 (52.8%) patients were unfrail at diagnosis, with a mean age of 56.72±7.11. 77.8% of the unfrail patients were less than 65 years old. 152 patients were frail at diagnosis, with a mean age of 59.47±8.28. 68% of the patients were less than 65 years old. There were statistical differences in age, DS stage, ISS stage and R-ISS stage between the two groups. (P < 0.05). After induction therapy, 246 patients (76%) rescored IMWG/ECOG frailty score before ASCT. 46 patients changed from frail state at first diagnosis to nonfrail before transplantation, mainly because of the improvement of ECOG score and renal function. There is no change from a nonfrail state at the first diagnosis to a frail state when entering the ASCT program. After logistics regression analysis of IMWG/ECOG score, age, renal function and CCI, unfrailty is the best indicator of selection patients as ASCT candidate, OR=0.37, 95%CI 0.21-0.63 (P < 0.001). At the time of ASCT, there was no significant difference in the ORR of induction therapy between frail and unfrail patients. But the granulocyte and platelet reconstruction during ASCT in the frail group was slower than that in the unfrail group, P<0.0001. The transplantation-related mortality was 0. In this cohort, the PFS and OS of the NDMM patients accepted VRD+transplantation was all better than those received VRD only. Most importantly, the OS of the frail patients scored at the time of ASCT was much poorer (P<0.05) than that of the unfrail group with no significant difference in PFS between two groups. But there were no significant differences in PFS and OS of the patients who changed from frail to unfrail after induction therapy compared with those remained unfrail at diagnosis and after induction therapy. Conclusion IMWG/ECOG frailty score can be used to select ASCT candidate for NDMM patients. In the study 144 patients (84.7%) remained unfrail at diagnosis and before transplantation accepted ASCT. and 46 frail patients (30.2%) at diagnosis transferred from frail to unfrail after induction and accepted transplantation. It was suggested that the IMWG/ECOG frailty score evaluated before transplantation is more instructive for long-term overall survival. The OS of unfrail patients was better than that of frail patients even with no significant difference in PFS.

t(11;14) is currently classified as a standard-risk genetic marker for newly diagnosed multiple myeloma (NDMM) patients. But some recent studies have suggested that t(11;14) may be an intermediate-risk marker in multiple myleoma (MM). The clinical significance of t(11;14) in MM is still controversial. Here, using high-resolution single nucleotide polymorphism-based mapping array (SNP-array) analysis and fluorescence in situ hybridization (FISH), the most common gained region of chromosome 11 was identified in 96/611 (15.7%) NDMM patients which located at 11q13.3-q25 (65.7Mb in size and contains 622 genes including CCND1). It demonstrated a statistically significant coexisting with t (11;14) (p<0.001), complex karyotypes (involves at least 6 chromosomes) (p<0.001), high plasma cell ratio in bone marrow (p=0.001) and poor response to VRD (bortezomib, lenalidomide, dexamethasone) treatment (p<0.001), but mutually exclusive with monosome 13, del(13q14), dup1q21 and t (4;14). When exploring the correlation of t(11;14) with genomic copy number variations (CNAs), it was also indicated that t(11;14) was most closely related to 11q gain (39%), while negatively correlated with others including gain of 1q and chromosome 3, 5, 6, 7, 9, 11, 15, 19, loss of 1p, 12p, 14q and chromosome 13 and 22. With a median follow up time of 22 months, survival analysis of 40 t(11;14) patients, 123 hyperdiploid (HRD) patients showed that 11q gain could have an adverse impact on the progression-free survival (PFS) in both groups. In t(11;14) subgroup, the median PFS (mPFS) were not reached, but PFS at 40 months were 60.9% vs 81.7% with 11q gain vs non-11q gain patients. In HRD subgroup, the mPFS were 23 months vs 49 months with 11q gain vs non-11q gain groups. Autologous hematopoietic stem cell transplantation (ASCT) can significantly improve the PFS of patients with t(11;14) and 11q gain (mPFS for transplant-eligible (TE) vs transplant-ineligible (TIE) patients were not reached vs 9 months, P=0.0067), but not helpful to 11q gain patients without t(11;14) (mPFS for TE vs TIE: 23 months vs 22 months, p=0.2137). Multivariate analysis confirmed that 11q gain was an independent adverse factor to PFS of MM with t(11;14) (Hazard ratio: 11.621, 95% CI: 1.027-131.507; p=0.048; n=37). Conclusions: Gain of 11q13.3-q25 is a reproducible chromosomal copy number abnormality in NDMM characterized by coexisting with t (11;14), complex karyotypes, higher plasma cell ratio in bone marrow and poor treatment response to VRD. t(11;14) patients with 11q gain had a poorer PFS compared to patients with t(11;14) only, mPFS was only 9 months for TIE patients. t(11;14) with 11q gain NDMM patients needs to be considered as high risk and ASCT could improve patients' survival.

Background: Despite the advent of numerously new drugs, multiple myeloma (MM) remains an incurable plasma cell malignancy. Autologous hematopoietic stem cell transplantation (ASCT) remains an important first line treatment for MM. In China, rate of utility of ASCT in front line was as low as 10%. There are many transplant-eligible (TE) patients who refuse ASCT for a variety of subjective and objective reasons,. Bortezomib, lenalidomide and dexamethasone (VRd) combination has been reported to demonstrate high efficacy in these patients (SWOG S0777), And recently, daratumumab combinations, such as D-VRd (GRIFFIN) and D-VTd (CASSIOPEIA), have shown good results in TE-NDMM patients who received ASCT as initial therapy. The observed benefits of these combination therapies have led us to explore the potential efficacy of D-VRd in standard risk TE-NDMM patients without ASCT. In addition, there were no studies assessing minimal residual disease (MRD) data after treatment with the D-VRd regimen in TE-NDMM patients who are unwilling to undergo ASCT in Chinese population , thus we chose MRD as the primary endpoint. This is the first open-label, single arm study to evaluate the efficacy and safety of D-VRd in TE-NDMM in standard risk without ASCT in China (NCT 05088330). Methods: This is a single-center prospective ongoing clinical study, planning to recruit 76 patients. NDMM patients as documented per IMWG criteria who were evaluated as transplant-eligible, but voluntary not to accept ASCT were enrolled. And t(4;14) or Del(17p) or t(14;16) or R-ISS stage III patients were excluded from this study. D-VRd regimen includes ‘daratumumab’ 16 mg/kg I.V. every week for 2 cycles, 16 mg/kg I.V. every 3 weeks for 6 more cycles, and then 16 mg/kg I.V. for 13 more cycles (Total: 21 cycles); ‘lenalidomide’: 25 mg, P.O., Days 1-14/1-8 cycles; ‘Bortezomib’: 1.3 mg/m2, SC, Days 1, 4, 8, 11/1-8 cycles; dexamethasone: 20 mg, P.O., Days 1, 2, 4, 5, 8, 9, 11, 12/1-8 cycles. The primary endpoint of this study was to evaluate the negativity of NGS MRD at 10-5 after 8 cycles of D-VRd. The secondary objectives of this study were to determine the ORR, sCR, ≥CR ≥VGPR, AE, TTR and DOR of treatment. Patients were recommended to have stem cells collection after 4 cycles of D-VRd treatment. Result: As of 30 June 2023, 24 patients including 6 safety-run-in patients were enrolled. The median (range) age of these 24 patients was 65 (50-74) years. 54.2% (13/24) were male. 62.5% of patients had a 1q gain. 16.7% (4/24) of patients had renal insufficiency with 30mL/min <CCR <60mL/min (Table 1). The median follow-up time was 3 (1-11) months, 8 patients completed 4 cycles and 2 patients completed 2 cycles. Among the 17 patients who had response evaluation, the ORR was 94.1%, 87.5% (7/8) of patients had VGPR or better after 4 cycles (Figure 1). All patients (6/6) above VGPR and CR had NGS MRD negativity. Both 2 patients who have completed the 8 cycles treatment achieved CR and MRD negativity. All patients had bone pain relief. The main treatment-related adverse events were hematological toxicity, which occurred in 22 patients including neutropenia (n=14, Grade 1-2 for 10 patients and Grade 3-4 for 4 patients), lymphopenia (n=13, Grade 1-2 for 10 patients and Grade 3-4 for 3 patients) and thrombocytopenia (n=19, Grade 1-2 for 15 patients and Grade 3-4 for 4 patients). One patient had to discontinue lenalidomide due to serious adverse event (SAE) of pulmonary embolism. Other toxicities to date include pneumonia (n=3, Grade 1 for 2 patients and Grade 2 for 1 patient), ALT/AST increase (n=10, all Grade 1), and rash (n=3). The infusion related reactions were reported in 25% of patients (n=6, Grade 1 for 4 patients and Grade 2 for 2 patients). Conclusion: In the safety-run-in phase, D-VRd induction therapy was well tolerated in the Chinese population in 6 patients. This preliminary study of D-VRd demonstrated excellent efficacy with rapid response even in a population with high 1q gain. The most common adverse events were hematological toxicities that were manageable after 2 cycles. The updated results will be presented in the following phase.

Background: Renal impairment (RI) is one of the common serious complications of MM. The DARE Phase 2 clinical study is daratumumab-based regimen for the treatment of MM patients with renal insufficiency, which is designed to use daratumumab in combination with dexamethasone for the treatment of RRMM with severe renal insufficiency. According to the updated data, after 8.3 months of follow-up, the 6-month PFS rate was 48.6%, ORR was 41.4%, renal response rate (RRR) was 20.7%. CASSIOPEIA phase III clinical study showed that with the extension of treatment time, the sCR rate and minimal residual disease (MRD) negative rate in D-VTd group were significantly improved compared with those in VTd group. According to the evidence from previous large phase III clinical trials of daratumumab in NDMM as well as its DARE phase II study and clinical case reports, daratumumab based treatment has a rapid onset of action in the treatment of MM patients with severe renal insufficiency, effectively response to the disease and improve the renal function of patients. An observational, multi-center, non-interventional study was designed to evaluate the safety and efficacy of daratumumab in combination with VTD in NDMM patients with renal dysfunction in real-world clinical practice. (NCT 05561049) Methods:NDMM patients older than 18 years and with a glomerular filtration rate(eGFR) of less than 40 ml/min were enrolled. Patients received VTD for C1, then go to DaraVTD for C2-4. The dose of Daratumumab was 16 mg/kg I.V. every week for 2cycles(cycles 2-3) , 16 mg/kg I.V. every 2 weeks for one more cycles;“Thalidomide”: 100 mg, P.O., Days 1-28/1-4 cycles;“Bortezomib”: 1.3 mg/m2, SC, Days 1, 4, 8, 11/1-4 cycles; Dexamethasone: 20-40mg, PO/I.V., qw/1-4 cycles. After induction therapy, patients entered consolidation therapy. Transplant eligable patients undergo stem cell collection and autologous stem cell transplantation followed by consolidation with DVTd regimen for 2 more cycles. Four more cycles of consolidation with DVTd were performed in transplant ineligible patients. The primary endpoint of this study is to evaluate VGPR+ rate after consolidation. The secondary endpoint is ORR, renal response rate (RRR), CR rate, MRD negativity after consolidation, and DOR, PFS, OS. NCI CTCAE V5.0 criteria were used to evaluate adverse events. Result: From Jan 1th to June 30 th 2023, 23 patients were enrolled. The median age of these 23 patients was 64 (34-78), 69.6%(16/23) was male.(Table 1) Among the 18 patients who have had response evaluation, the ORR was 94.4%. median onset time of response was 2 months. After induction therapy, the ORR was 100%, 50% patients had gotten CR. After consolidation, All patients were above VGPR and CR and were NGS MRD negative.55.5% patients(10/18) achieved renal remission after one cycle, while 86.7% after 2 cycles, 91.7% after 3 cycles and 100% after 4cycles. Among the 20 patients who have had adverse events evaluation. The main treatment-related adverse events were hematological toxicity, including neutropenia (n=10/20, grade 1-2 for 6 pts and grade 3-4 for 4 pts), lymphopenia (n=5/20, grade 1-2 for 5 pts) and thrombocytopenia (n=8/20, grade 1-2 for 6 pts and grade 3-4 for 2 pts). One patient with acute pancreatitis had to stop treatment. Other toxicities to date included pneumonia (n=5/20, grade 1 for 4 pts and grade 2 for 1 pts), peripheral neuropathy (n=10/20, grade 1 for 7 pts and grade 2 for 3 pts), and rash(n=5). The infusion related reactions were 37.5%(n=6/18, grade 1 for 4 pts and grade 2 for 2 pts). Conclusion: In Chinese NDMM patients with RI, quad-drug induction of DVTD with/without ASCT consolidation showed nice tolerability and high overall response of disease even with a high percentage of high-risk patients. This preliminary study also suggested excellent efficacy with rapid improvement in renal function. The most common adverse events were hematological toxicity. Updated results will be presented at the following phase.

Background Cardiac amyloidosis was thought to be a rare disease, but the data shows that its prevalence rate is increasing, and the light chain (AL) cardiac amyloidosis are the most common and worst [1]. Because of the lack of symptoms specificity in the preliminary stages of AL cardiac amyloidosis, resulting in underdiagnosis or severe delays in diagnosis, patients are often delayed in the optimal timing of treatment. A considerable proportion of patients are diagnosed after the onset of symptoms of heart failure which progresses rapidly and results in poor prognosis and high mortality. Patients have a mortality rate of up to 50% within 4-6 months after diagnosis of congestive heart failure and the median survival of these patients were less than 12 months [2]. Therefore, early diagnosis and treatment are particularly important for them. Speckle tracking echocardiography has a good imaging analysis of cardiac amyloidosis, which remains the most often used imaging tool. This study aimed to explore the use of speckle tracking echocardiographic parameters to build models which improve the diagnostic rate of patients with suspected AL cardiac amyloidosis and assess the prognosis of patients with AL cardiac amyloidosis. Methods We studied twenty-four patients of pathologically confirmed amyloidosis from March 2017 to February 2023 at the First Affiliated Hospital of Soochow University. According to the criteria for organ involvement, patients were divided into two groups based on whether the heart was involved or not and SPSS 26.0 was used to analyze data. The differences of characteristics and various parameters of Speckle tracking echocardiography between two groups were compared and the indicators with statistical difference were selected for single factor analysis and multivariate analysis. Statistically significant factors were used to establish diagnosis and prognosis assessment models as below. Result In this study, the rate of cardiac involvement was 62.5%. Until June 30 th, 2023, median follow-up time of twenty-four patients was 31 months, and the 5-year survival rate was 74% in CA group and 85.7% in non-CA group. Characteristics The results showed that CA group has lower baseline blood pressure, and the levels of NT-pro BNP and dFLC were significantly higher in the CA group compared to the non-CA group. In speckle tracking echocardiography parameters, CA group has significantly increased IVSd, LVPWd, RWT, E/e and decreased EF, interventricular septum e', lateral wall e' and left ventricular global strain. Diagnosis The results showed that CA group is more likely to be involved in the heart when monoclonal proteins are formed in the peripheral blood （OR=0.031, 95%CI 0.003-0.365, P=0.002）. In univariate analysis, E/e>10.85, interventricular septum e‘<5.25 cm/s, lateral wall e‘<6.05 cm/s, |left ventricular global strain|<16.3% and left ventricular diastolic function ≥Class II have the effect on CA group with statistically significant. Incorporating them into variables to construct a multivariate logistic regression model showed that: the model was built successfully (Omnibus test: P<0.001) and the goodness of fit model is well (Hosmer-Leme show test: P=1). 88.9% of the study subjects who were CA patients were predicted by the model to be CA patients, while 92.9% of the study subjects who were not CA patients were predicted by the model to be not CA patients, but the 5 factors had no significant effect on cardiac amyloidosis (P > 0.05). Prognosis assessment The result of the study shows that IVPWd>13.5mm, RWT> 0.51, NT pro-BNP>6614pg/mL and dFLC>142.35mg/L are elevated risk factors for prognosis with statistically significant. (Figure1). They were included in the variables to construct a multi-factor Cox proportional hazards model and it turns out: the model was built successfully (Omnibus test: P<0.05), but these 4 factors had no significant effect on cardiac amyloidosis (P > 0.05). Conclusion Speckle tracking echocardiography is of great value in the diagnosis and prognosis of patients with cardiac amyloidosis. The combined analysis of echocardiography parameters and serological abnormalities can help in the diagnosis and prognostic assessment of the disease, it also helps to identify patients with poor prognosis early and increasing the possibility of future treatment strategies based on risk stratification.

Objective:To investigate the clinical characteristic of patients infected with influenza A virus, and evaluate the influencing factors of influenza A pneumonia.Methods:The clinical characteristics and treatment of 160 inpatients with influenza A virus infection from 2016 to 2020 in the First Affiliated Hospital of Zhengjiang University School of Medicine were retrospectively analyzed, and the influencing factors of influenza A pneumonia were analyzed by multiple Logistic regression.Results:The main symptom of influenza A patients was fever (159 cases, 99.38%). There were 121 cases(75.63%) complicated with influenza A pneumonia and 157 cases(98.13%) treated with antiviral therapy. The factors influencing the complications of pneumonia in patients with influenza A were lactate dehydrogenase(LDH) ( OR=1.010, 95% CI: 1.003-1.017) and C-reactive protein(CRP) ( OR=1.091, 95% CI:1.034-1.150). Conclusions:Fever is the most common symptom of influenza A, and viral pneumomia is a common complication. CRP and LDH can be used as reference indexes to evaluate the severity of influenza A patients.

目的 研究非暴力危机干预运用于精神病患者中的价值及对约束率的影响.方法 选择重庆市第十一人民医院2017年7月-2019年3月收治的600例精神病患者作为实验对象,遵照随机数字表法随机分成实验组和对照组各300例,实验组给予非暴力危机干预,对照组给予常规约束护理,对比两组干预结果.结果 实验组平均约束次数、每次约束时长均低于对照组(P＜0.05).实验组保护约束率22.00％明显高于对照组36.00％(P＜0.05).干预前两组的BPRS评分相比无意义(P＞0.05),干预后两组评分均明显降低,但实验组改善程度优于对照组(P＜0.05).实验组在沟通方式、信息获取、延续性护理及整体评价上的满意度高于对照组(P＜0.05).结论 非暴力危机干预运用于精神病患者中效果显著,能够有效降低约束率,快速稳定病情,患者满意度较高,维持良好护患关系.

The present study aimed to determine whether 18F-FDG PET/CT performed before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) can predict clinical outcomes in acute leukemia (AL). A total of 79 examinations comprising 72 patients with AL who underwent 18F-FDG PET/CT before and/or after allo-HSCT were retrospectively enrolled between January 2011 and January 2019. Outcomes were assessed using overall survival (OS) and disease-free survival (DFS). A total of 63 examinations were PET-positive, while 16 examinations were PET-negative. Increased BM and splenic 18F-FDG uptake were observed in 24 (19/79) and 14% (11/79) of examinations, respectively. 18F-FDG-avid lymph nodes were observed in 38% (30/79) of examinations. ENEMES involvement was detected in 44% (35/79) of examinations. The presence of ENEMES involvement [OS hazard ratio (HR), 6.399; 95% confidence interval (CI), 1.843-22.224; P=0.003; post-HSCT OS: HR, 7.203; 95% CI, 1.510-34.369; P=0.013; DFS HR, 3.671; 95% CI, 1.145-11.768; P=0.029], post-transplantation minimal residual disease (DFS HR, 4.381; 95% CI, 1.594-12.040; P=0.004; pre-HSCT OS HR, 11.455; 95% CI, 1.336-98.179; P=0.026) and disease status (OS HR, 0.330; 95% CI, 0.128-0.848; P=0.021; post-HSCT OS HR, 0.195; 95% CI, 0.050-0.762; P=0.019; DFS: HR, 0.278; 95% CI, 0.091-0.851; P=0.025) could serve as an adverse prognostic factor in patients with AL treated with allo-HSCT. 18F-FDG PET/CT before and/or after allo-HSCT was a predictor for OS and DFS in patients with AL. ENEMES involvement detected using 18F-FDG PET/CT may help identify patients with AL who are likely to have unfavorable clinical outcomes.

Abstract Rationale: The incidence of extramedullary plasmacytoma (EMP) accounts for 3% to 4% of all cases of generalized plasmacytoma. The most common pathogenic sites are the head and the neck. It is noteworthy that the pathogenic site in this case is extraperitoneal, which is uncommon in clinical practice. In this case report, we aim to discuss the clinical features and diagnosis as well as the treatment methods of EMP. Patient concerns: A 30-year-old female was admitted to our hospital due to a palpable right upper abdominal mass without symptoms of abdominal pain, diarrhea, constipation, fever, or oliguria. Diagnosis and interventions: Enhanced CT scan showed a right retroperitoneal mass, which we considered to be isolated fibroma. Multiple myeloma (MM) was excluded through whole-body diffusion weighted imaging (DWI) and bone marrow biopsy. The patient underwent retroperitoneal tumor resection, and the postoperative pathology revealed plasmacytoma. Thereafter, she received only postoperative radiotherapy. Outcomes: During the radiotherapy, the patient's condition and appetite were acceptable with I° gastrointestinal reaction. The CT examination of the chest and upper abdomen performed 4, 8, and 12 months after the radiotherapy still showed postoperative and postradiotherapy changes after retroperitoneal plasmacytoma resection without obvious abnormal signs. No recurrence and metastasis were detected after a one-year follow-up. Lessons: Retroperitoneal extramedullary plasmacytoma (EMP) is a rare condition that is frequently a diagnostic challenge, mainly due to its unusual location and nonspecific symptoms, especially in the early stages. The diagnosis of EMP is made through a combination of imaging and pathological examination. Presently, the combinations of radiotherapy and surgery or radiotherapy are the primary treatments, usually leading to an acceptable local control rate. The application of chemotherapy, however, should be carefully considered.

Objective To investigate the efficacy and safety of rituximab (RTX) as first-line treatment of acquired thrombotic thrombocytopenic purpura (aTTP). Methods Twenty-five patients with acute aTTP and/or severe a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency were admitted to our centre from April 2009 to March 2015. Fourteen patients received RTX plus standard therapy (plasma exchange and corticosteroids) at acute episodes. Haemoglobin, platelet count, schistocytes, lactate dehydrogenase levels, ADAMTS13 activity and its inhibitors, and the ratio of B lymphocytes in the peripheral blood, were monitored. The number of plasma exchange (PEXs), total plasma volume, remission time, relapse ratio, and adverse effects were recorded. Results The median number of PEXs was 5 (2-17) sessions and median total plasma volume was 168.43 ml/kg (62.86-469.52 ml/kg). Patients achieved haematological remission at a median of 15 days (5-22 days), and the median time of immunological remission was 2 weeks (2-8 weeks) with a median follow-up of 13 months (3-61 months). ADAMTS13 activity significantly increased after 2 weeks. The B lymphocyte percentage in peripheral blood was reduced 1 week after the first dose of RTX infusion compared with before treatment (2.21% ± 5.23% vs 18.47% ± 7.34%, P = 0.000 [the result of statistical software]), and began to gradually increase 9 months later. Severe adverse effects and relapsing TTP were not observed during therapy and follow-up. However, one patient who had sustained immunological remission died of severe pneumonia 7 months later. Conclusion Although our study was limited by its small sample number and it was a non-controlled, clinical trial, it showed potential benefits of RTX therapy for acute aTTP. RTX may be administered as a first-line therapy for lowering patients' relapse rate in the long term. Randomized, controlled trials of RTX for aTTP are required.

Linear IgA bullous dermatosis (LABD) is a rare auto-immune bullous disease occurring in adults or childhood. There are similarities and differences between these two subtypes of the disease. We report a twenty-seven-year-old patient with adult subtype of LABD. The disease started from the second month of gestation and remitted after the delivery.

目的：研究老年精神科患者的临床特点及护理干预。方法以2011年6月～2015年6月在我院收治的90例老年精神科患者为研究对象，回顾性分析所有患者疾病资料，以说明老年精神科患者的临床特点，并在此基础上，实施相应的护理干预措施。结果90例患者中25例器质性精神障碍、46例精神分裂症、19例心境障碍；无死亡发生，治疗有效率为87%，预后较好。结论老年精神科患者进行临床特点的研究有利于患者早期诊断和治疗措施的制定及实施，护理干预能有效地促进患者康复，值得临床深入推广和完善。