Cell division cycle 20 homolog (CDC20), a critical substrate-recruiting subunit of the anaphase-promoting complex/cyclosome (APC/C), binds to APC/C to form the active APC/C-CDC20 complex, which regulates the degradation of key cell cycle substrates to ensure accurate and timely mitotic progression. Accumulating evidence demonstrates that CDC20 functions as an oncogenic factor, with its overexpression observed in various malignancies. Its dysregulation is closely associated with tumor initiation, progression, drug resistance, and poor clinical outcomes, underscoring its potential as a therapeutic target in anti-cancer strategies. In this review, we describe the biological functions of CDC20 in cancers, discuss its role and underlying mechanisms in solid tumors and hematological malignancies, and elucidate currently reported CDC20-targeted inhibitors along with their clinical benefits and challenges. By emphasizing the oncogenic significance of CDC20, we propose that the development of specific, safe, and potent CDC20 inhibitors could provide a promising therapeutic approach for cancer patients exhibiting CDC20 overexpression.

Selinexor, a selective nuclear export inhibitor, blocks exportin-1 and reduces oncoprotein messenger RNA translation, and is approved for the treatment of relapsed/refractory multiple myeloma in combination with proteasome inhibitors, immunomodulators, anti-CD38 antibodies, etc. Nevertheless, selinexor presents limited monotherapy efficacy with an objective response rate of 29% and fails to completely overcome drug resistance. To improve the therapeutic outcome, this study investigated the combined treatment of selinexor and a CD73 inhibitor in a murine tumor model. The expression of CD73 in multiple tumor cell lines following selinexor treatment was first analyzed. In vivo experiments were performed on J558-inoculated BALB/c mice, which were divided into vehicle group, ATG-037 (CD73 inhibitor) monotherapy group, ATG-010 (selinexor) monotherapy group, and combination therapy group. Single-cell RNA sequencing (scRNA-seq) was utilized to characterize immune cell subtypes and tumor-immune crosstalk, and immunofluorescence staining was conducted on histological tumor samples. In addition, a co-culture model of CD8+ T cells and multiple myeloma cell lines was established to verify the synergistic anti-tumor effect and underlying mechanism of the combined regimen. The results demonstrated that selinexor treatment upregulated CD73 expression in the majority of tumors. The combination therapy remarkably suppressed tumor growth with an inhibition rate of 62%, which was superior to the monotherapy of ATG-037 (31%) and selinexor (43%). scRNA-seq analysis revealed that the combination treatment synergistically potentiates CD8+ T cell activation by enhancing the interaction between CD8+ T cells and Enpp1 cells via the CD80-CD28 signaling pathway, and the increased infiltration of CD8+ T cells in tumor tissues of the combination group was further validated by immunofluorescence staining. Co-culture experiments further confirmed that CD73 inhibition strengthens selinexor-mediated tumor cell killing by activating CD8+ T cells, as evidenced by significantly elevated levels of Granzyme B (P = 0.0252) and IFN-γ (P = 0.0067). In conclusion, CD73 inhibition enhances the anti-myeloma efficacy of selinexor by specifically activating CD8+ T cells and ultimately promoting the apoptosis of multiple myeloma cells.

Cell-free DNA in blood originates from fragmented chromatin released by dying cells from both healthy and diseased tissues1,2. These fragments carry rich molecular modalities that can reveal pathological alterations in tissues of origin3-10. Here we develop cf-EpiTracing, a highly sensitive automated platform that profiles histone modifications in cell-free DNA from as little as 50 μl of human plasma. By integrating multimodal chromatin states with machine learning, cf-EpiTracing enables accurate deconvolution of cell types of origin. We generated 2,417 cf-EpiTracing profiles from plasma of 125 healthy individuals and 549 patients with inflammatory bowel disease, colorectal cancer, coronary heart disease or lymphoma. cf-EpiTracing enabled unbiased identification of primary diseased tissues and other organ involvement, stratification of B cell lymphoma subtypes with different genetic and epigenetic underpinnings, and detection of early-stage diseases or lesions. Surveying dynamics of epigenetic signatures uncovered disease transformation from follicular lymphoma to diffuse large B cell lymphoma. Further, cf-EpiTracing revealed genomic translocations and epigenetic alterations in patients with mantle cell lymphoma. Of note, our study leverages holistic epigenetic signatures, independently of knowledge of gene transcription, to accurately report recurrence risk and therapeutic response. Together, these findings establish cf-EpiTracing as an automated, non-invasive, epigenome-centric framework with broad applications in early diagnosis, molecular subtyping and prognostic prediction.

We retrospectively evaluated the efficacy and safety of zanubrutinib combined with age-adapted bendamustine and rituximab followed by zanubrutinib maintenance in 23 elderly patients with mantle cell lymphoma (MCL). Patients received six induction cycles of this regimen, followed by zanubrutinib maintenance for ≥2 years. After induction, the complete response rate was 73.9% and the overall response rate was 91.3%. The 24-month progression-free survival rate was 75.4% and the overall survival rate was 90.7%. Undetectable minimal residual disease (uMRD) was achieved in 88% of patients after induction and increased to 94% during maintenance. CD4 + T cell and NK cell counts declined to nadir post-induction but recovered by 12 months. Zanubrutinib combined with age-adapted bendamustine and rituximab, followed by zanubrutinib maintenance, is an active and feasible regimen for elderly patients with MCL, offering a potential treatment option in clinical practice.

Introduction Mantle cell lymphoma (MCL) constitutes an aggressive subtype of B-cell lymphoma and demonstrates significant clinical and biological heterogeneity. B symptoms are important clinical indicators in tumors. In the present study, we investigated the frequency and prognostic significance of B symptoms among different primary sites of MCL. Method We conducted an observational study of 2,025 MCL patients from the SEER database. We analyzed the frequency of B symptoms at different primary sites and evaluated their impact on prognosis. Results The highest incidence of B symptoms was observed in the small intestine (35.29%), and the lowest in the nasopharynx (6.67%). Among patients with primary lymph node involvement, the intrathoracic and abdominal lymph nodes showed the highest proportion of B symptoms (both 40%), while the head, face, and neck lymph nodes showed the lowest (9.3%). In patients with primary site involvement of lymph nodes or nasopharynx, those with B symptoms had a worse prognosis than those without B symptoms (P < 0.05). Similarly, patients with primary lesions involving multiple regional lymph nodes, lymph node not otherwise specified (NOS), or inguinal/leg lymph nodes exhibited worse prognosis when B symptoms were present (P < 0.05). Conclusion In summary, our study highlights the heterogeneity in both the frequency and prognostic significance of B symptoms across different primary sites in MCL patients.

Mantle cell lymphoma (MCL) is an uncommon and aggressive type of B-cell non-Hodgkin lymphoma, wherein TP53 mutations play a critical role. This study analyzed the effect of different TP53 mutations on the clinical characteristics and prognosis of patients with MCL. TP53 sequencing data and clinical and prognostic information were collected from 215 patients with MCL treated at Peking University Third Hospital between August 2017 and December 2022. Furthermore, descriptive and Cox regression analyses were also performed. Our findings revealed the association between TP53 mutations and higher Ki67 levels (p = 0.008), elevated combined MCL International Prognostic Index (MIPI-c; p = 0.032), blastoid/pleomorphic subtypes (p = 0.020) and ≥ 2 treatment lines (p = 0.026). Missense mutations (75.6

OBJECTIVE:To investigate the efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) in the treatment of mantle cell lymphoma (MCL) in the real world. METHODS:The clinical data of 85 MCL patients who underwent ASCT in Peking University Third Hospital and other Chinese centers from January 2005 to December 2021 were retrospectively analyzed. The patients were treated with rituximab-based chemotherapy before transplantation, and the effects of clinical characteristics, treatment regimens and biological indicators on overall survival (OS) and progression-free survival (PFS) were observed. RESULTS:Among the 85 patients, there were 65 males and 20 females with a median age of 53 (34-68) years, 11 cases of blastic and pleomorphic type and 74 cases of classical type. According to Ann Arbor staging, 5 cases were in stage I-II and 80 cases were in stage III-IV. There were 18 cases with Ki-67≥50%, 29 cases with B symptoms, and 68 cases with external involvement. High-dose cytarabine was used in 56 patients, and 31 patients were in a relapsed/refractory state. With a median follow-up of 51 (12-202) months after ASCT, the estimated 5-year PFS rate was (68.4±6.0)%, and the estimated 5-year OS rate was (87.4±4.6) %. Multivariate Cox regression analysis showed that MIPI-c intermediate-high/high risk (HR=4.461, 95%CI : 1.822-10.918, P =0.001) and no maintenance treatment (HR=3.127, 95%CI : 1.398-6.991, P =0.005) were independent adverse prognostic factors for PFS, and relapsed and refractory state(HR=4.727, 95%CI : 1.005-22.234, P =0.049) were independent adverse prognostic factors for OS. CONCLUSION:ASCT consolidation therapy plays an important role in improving PFS and OS of MCL patients with young age and good general condition, especially for those with MIPI-c low/low-intermediate risk, receiving maintenance therapy with new drugs after ASCT, and non-relapsed/refractory state.

Although targeting the ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1) has shown promise in treating a number of diseases, its function in mantle cell lymphoma (MCL) and its regulatory connection to SOX11 are yet unknown. Our study showed that UHRF1 is markedly upregulated in MCL, and this overexpression is associated with a poorer overall survival rate in MCL patients. Furthermore, in clinical MCL specimens, UHRF1 showed a positive correlation with the expression of SOX11 and Ki-67. In vitro, UHRF1 knockdown induced apoptosis and caused G2/M-phase arrest while functionally suppressing MCL cell motility, invasion, and proliferation. In MCL xenograft models, UHRF1 silence significantly delayed tumor development, and pharmacological targeting UHRF1 with CM272 effectively inhibited MCL progression with a tolerable safety profile. Mechanistically, SOX11 drives the transcriptional activation of UHRF1 by directly binding to its promoter region. Our results reveal that the SOX11-UHRF1 regulatory axis is a critical modulator of tumor cell growth and proliferation and identify UHRF1 as a key oncogenic driver in MCL. Additionally, CM272’s antitumor effect was validated in preclinical MCL animal models while exhibiting an acceptable safety profile.

Cell division cycle 20 homologue (CDC20), a key regulator of mitosis, is frequently overexpressed in cancers and linked to tumor progression. However, its role in mantle cell lymphoma (MCL) remains unclear. This study explored the functional significance of CDC20 in MCL and its underlying mechanisms. CDC20 expression was analyzed in peripheral blood mononuclear cells (PBMCs), bone marrow mononuclear cells (BMNCs), clinical samples, and MCL cell lines (Z138, Mino, Rec1), followed by correlation with clinicopathological features. MCL cells were treated with the CDC20 inhibitor apcin or transduced with CDC20-knockdown lentivirus, and effects on proliferation, apoptosis, cell cycle, migration, and invasion were assessed. The anti-tumor effect of apcin was tested in the Z138-driven xenograft mouse model. RNA-seq was performed to identify signaling pathways altered upon CDC20 inhibition, and western blot (WB) analysis confirmed the dysregulation of key pathway components. Consequently, CDC20 was significantly upregulated in PBMCs, BMNCs, tumor tissues, and MCL cell lines compared to their respective controls. Apcin or CDC20 knockdown suppressed proliferation, migration, and invasion while inducing apoptosis and G2/M arrest in MCL cells. In vivo, apcin effectively and safely inhibited tumor growth. RNA-seq revealed differential genes were enriched in the PI3K/AKT signaling pathway. WB validated reduced PI3K/AKT phosphorylation levels after CDC20 inhibition, suggesting CDC20 promoted the malignant phenotype of MCL via PI3K/AKT signaling. Therefore, CDC20 plays a critical role in MCL pathogenesis. Targeting CDC20 and the PI3K/AKT pathway may offer a promising therapeutic strategy for MCL.

Primary gastrointestinal lymphoma (PGIL) comprises histologically diverse extranodal lymphomas with markedly different biological characteristics and clinical outcomes. This study evaluated the association between pretreatment serum cytokine concentrations and clinical outcomes in PGIL, with particular attention to interleukin-10 (IL-10). We retrospectively reviewed 165 adults with PGIL treated between 2012 and 2022. Pretreatment serum cytokine measurements were available for 85 patients, who comprised the cytokine cohort. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Serum IL-10 was analyzed as a log-transformed continuous covariate in Cox proportional-hazards models. Conventional receiver operating characteristic (ROC) analysis of vital status was performed as an exploratory assessment of discrimination for overall mortality. Histology-stratified IL-10 distributions, a DLBCL-specific continuous Cox analysis, and a sensitivity analysis excluding MALT and follicular lymphoma were also performed. In the full cohort, the reverse Kaplan–Meier median follow-up was 33.4 months, and the 3-year OS rate was 85.1

Background: Ferroptosis, an iron-dependent form of regulated cell death, has been implicated in tumor biology and cancer immunotherapy, but its pan-cancer landscape and impact on the tumor microenvironment (TME) and treatment response remain incompletely defined. We aimed to establish the ferroptosis signature (Fp.Sig) as a quantitative ferroptosis index within the pan-cancer single-cell landscape, thereby guiding clinical patient stratification and therapeutic decision-making. Methods: We integrated profiles of 10 510 bulk samples across 33 The Cancer Genome Atlas cancer types, along with a large-scale single-cell analysis comprising 3 289 156 cells from 1559 samples across 19 cancer types, sourced from the Curated Cancer Cell Atlas and CancerSCEM. Furthermore, we incorporated CRISPR-Cas9 dependency screens targeting 17 387 genes in 378 cell lines, pharmacogenomic data covering 345 drugs in 738 cell lines, and 13 clinical trials involving 1091 patients treated with immune checkpoint inhibitors. The prognostic and predictive value of Fp.Sig was assessed through modeling and external validation in both comprehensive and prospective cohorts. Results: We developed Fp.Sig at the bulk multi-omics and single-cell resolution pan-cancer level by using 10 machine learning algorithms and 101 algorithm combinations. Fp.Sig stratified patients into molecular subgroups with distinct overall survival and retained independent prognostic significance after adjustment for age, sex, and stage. Higher Fp.Sig was associated with elevated genomic instability, oncogenic pathway activation, virus-related tumor states, and distinct telomere phenotypes. Increasing Fp.Sig correlated with greater lymphocyte infiltration but a more immunosuppressive TME enriched for regulatory T cells and myeloid-derived suppressor cells. Single-cell analysis revealed coordinated signatures in malignant and immune cells and identified VEGFA-NRP1 signaling between ferroptosis-high tumor cells and myeloid populations, implicated in TME remodeling. Fp.Sig was linked to oncogenic mutations, ferroptosis-related metabolic reprogramming, and differential sensitivity to targeted agents, including the TOP1 inhibitor SN-38. Lower Fp.Sig was associated with improved survival and higher response rates, and an Fp.Sig-based response model achieved an AUC of 0.78 in validation, with competitive or improved discrimination versus established predictors in both comprehensive cohorts and prospective cohorts, which demonstrates its potential to assist clinical decision-making. Conclusions: These data define a pan-cancer ferroptosis atlas and provide a ferroptosis score and web tool that may support risk stratification and therapeutic decision making (https://puh3.shinyapps.io/FpSig_predict/).

[This corrects the article DOI: 10.3389/fmed.2026.1751344.].

Background:Mantle Cell Lymphoma (MCL) is a subtype of B-cell lymphoma characterized by varied clinical manifestations. The immune status is associated with MCL's development and outcome. This study aims to evaluate the prognostic value of peripheral cytokines and blood lymphocyte subsets in MCL patients. Methods:This retrospective study analyzed patients' clinical characteristics, treatment strategies, progression-free survival (PFS), and overall survival (OS). Immune cell levels and cytokines were evaluated via peripheral blood flow cytometry. Prognostic models incorporating immune characteristics were developed using XGBoost algorithms. Results:The study involved 78 MCL patients with a median follow-up period of 40 months. The median PFS and median OS were 32 and 48 months. Univariate analysis linked poor PFS to factors including elevated β2-MG, Ann Arbor stage III-IV, low albumin levels (<35 g/L), high SUVmax (≥11), reduced T cells (<70.42%), reduced CD4 + T cells (<34.63%), and increased NK cells (≥8.37%). Factors linked to poor OS included the pleomorphic and blastoid subtypes, albumin below 35 g/L, and high SUVmax (≥11). Multivariate analysis identified high SUVmax (≥11) as an independent predictor of poor PFS and OS in MCL patients. XGBoost regression and classification models were developed to determine feature importance, highlighting five key features: SUVmax, LDH, IL-2, TNF-α, and CD4 + T cells. A prognostic model using these immune features was created to predict patients' PFS, dividing them into high-risk and low-risk categories. This model showed superior discriminatory power compared to the MIPI and MIPI-C models and had comparable calibration ability. Conclusion:This study developed an innovative immune prognostic model for evaluating the prognosis of MCL patients, integrating immune factors with existing clinical features to improve prognostic evaluation.

Primary testicular lymphoma (PTL) is a rare but aggressive form of extranodal lymphoma with a high risk of central nervous system (CNS) relapse and poor long-term survival. However, the optimal CNS prophylaxis strategy and effective prognostic models for PTL remain unclear. This study aimed to evaluate the prognostic impact of intrathecal (IT) prophylaxis and to develop a novel, simplified prognostic model in a Chinese multicenter cohort. We retrospectively collected data from a total of 55 patients with PTL, treated at three major tertiary hospitals in China. Multivariate Cox regression identified independent prognostic factors for overall survival (OS) and progression-free survival (PFS). A new risk stratification model (BL model, based on B symptoms and LDH levels) was constructed and validated using time-dependent C-index and calibration plots, and compared with the International Prognostic Index (IPI). IT prophylaxis reduced CNS relapse rates (9.1

Glofitamab is a novel bispecific antibody targeting CD20×CD3, capable of simultaneously targeting CD20 and CD3 to activate T cells and release cytotoxic proteins that kill cancer cells. Cytokine release syndrome (CRS) is one of the most common adverse events observed in clinical trials of glofitamab. In most cases, CRS is mild, transient, and manageable with appropriate treatment. This paper reports a case of persistent CRS in a patient with mantle cell lymphoma following glofitamab treatment and reviews the relevant literature for reference.

BACKGROUND AND AIMS:Mantle cell lymphoma (MCL), an uncommon lymphoma subtype, is clinically characterized by its heterogenous behavior. Established prediction system including several clinical and biological parameters can help in determining the aggressiveness of MCL in younger patients. However, there are limited parameters on predicting the clinical outcome of older patients. The present study was performed to identify the prognostic factors and optimal treatment modalities in older Chinese MCL patients. METHODS:Patients (age ≥ 65 yrs) with MCL from 19 comprehensive hospitals in China were included. Clinical characteristics, therapeutic strategies, progression-free survival (PFS) and overall survival (OS) time of these patients were collected. RESULTS:Totally, 259 eligible patients were enrolled. The median age of patients was 69 years (range, 65-88). The median of PFS and OS were 29 months (95%CI: 26-37) and 76 months (95%CI: 61-96) months, respectively. Multivariate regression analysis determined that ECOG score ≥ 2, high MIPI score and absence of maintenance treatment were independently associated with poorer PFS of MCL patients; while ECOG score ≥ 2 and absence of maintenance treatment were independently correlated with a poorer OS. Patients with MCL who received BTKi-containing regimens or maintenance therapy showed significantly longer PFS and OS than those who did not receive these therapies. Maintenance treatment can improve the survival rate of older patients with MCL regardless of TP53 status. CONCLUSIONS:ECOG ≥ 2, high MIPI score, and absence of maintenance therapy were associated with poorer survival outcomes for older Chinese MCL patients. Maintenance therapy and BTKi-containing regimens have been shown to increase the survival rate of older Chinese MCL patients.

Objective:To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation(ASCT)for the treatment of primary central nervous system lymphoma(PCNSL).Methods:In a retrospective,single center,single arm study,we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation(HDC-ASCT)at our center from March 2021 to December 2024.The clinical characteristics of the patients,the conditioning regimen details,treatment-related toxicities and adverse reactions,post-transplant disease remission status,and survival outcomes were analyzed.Results:A total of 28 patients were included.Among them,19 patients received ASCT as first-line consolidation therapy in complete response(CR)or partial response(PR)status,and 9 patients with relapsed/refractory disease underwent salvage ASCT.The median time to neutrophil engraftment was 9 days(range:5-11 days),and the median time to platelet engraftment was 10 days(range:6-13 days).All patients achieved CR at the initial efficacy evaluation post-ASCT.The main complications during the transplantation period were febrile neutropenia(26 cases)and grade 3 diarrhea(9 cases).No transplantation-related mortality occurred.Post-ASCT,19 patients received maintenance therapy,which was demonstrated to be safe and effective.Three patients relapse,and one patient died.The median progression-free survival(PFS)and overall survival(OS)of patients were not reached.The estimated 1-year and 2-year cumulative PFS rates were 88.4％and 66.3％,respectively,while the 1-year and 2-year OS rates were both 94.1％.Conclusion:The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.

Patient-reported health-related quality of life (HRQoL) impacted by symptom burden is predictive of overall survival in patients with aggressive Non-Hodgkin lymphoma (NHL). This cross-sectional study investigated the Core Symptoms Burden Set (CSBS) significantly affecting the HRQoL in patient with aggressive NHL and identify a single cutoff point to separate clinical difference. The MDASI-TCM and EQ-5D-5 L were used to assess the symptom (severity and interference) and HRQoL. The t test, chi-square test or Wilcoxon rank-sum test were used to determine differences in symptoms burden between during and after cancer therapies. A multivariate linear regression model was used to identify associations between the CSBS and HRQoL. Receiver operating characteristic curves were used to identify optimum cutoff point considered the grading scale (0 vs. 1–3) of the ECOG as the anchor. Total 116 eligible patients with aggressive NHL were analyzed. The CSBS were disturbed sleep (47.4

P53 mutation (TP53m) is a common intrinsic factor involved in relapsed or refractory (R/R) B cell malignancies that associates with treatment resistance. As a novel immunotherapy, CAR-T has been increasingly applied in TP53m B cell malignancies, yet whether it can overcome the poor outcome of the TP53m population is controversial. We searched MEDLINE and EMBASE to identify population-based cohort studies that evaluated the CAR-T treatment outcomes between wild type and TP53m patients in B cell malignancies. Meta-analysis on their complete response (CR), partial response (PR), overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) was carried out and pooled risk ratios (RR) or hazard ratios (HR) were estimated. A total of 10 eligible studies reporting 848 patients with B cell malignancies from wild type and TP53m groups receiving CAR-T therapy were selected. The CR and ORR were comparable in both wild type and TP53m patients either with B cell lymphoma or leukaemia (all p > 0.05). However, the TP53m group was associated with shorter PFS and OS in both diseases (all p < 0.05). In traditional single targeting CAR-T therapy, the PFS and OS were shorter in the TP53m group than in the wild type group (all p < 0.05). In contrast, the former outcomes of the wild type and TP53m groups were comparable when receiving dual-targeting CAR-T treatment (all p > 0.05). Though the CR and ORR of wild type and TP53m groups were similar, the PFS and OS of B cell malignancy patients bearing TP53m were inferior to wild type patients receiving CAR-T cell treatment. Notably, the CR, PFS and OS of wild type and TP53m groups exhibit the same therapeutic effect via CD19/22 CAR-T cocktail therapy. In other words, the poor prognosis of TP53m patients may be overcome by double targeting CAR-T mode.

Background: IM19 is an autologous, CD19-directed, chimeric antigen receptor (CAR) T-cell product, which is manufactured in China using a commercial process. We aimed to evaluate the efficacy and safety of IM19 in patients with relapsed or refractory mantle cell lymphomas in a Phase I clinical study. Methods: A phase 1 clinical trial has been launched to evaluate the safety and efficacy of IM19 for the treatment of relapsed/refractory MCL. We enrolled adult patients (aged ≥18 years) with relapsed or refractory MCL who had received at least 2 prior treatment regimens(including BTK inhibitor). Patients were assigned to one of two target dose levels of IM19 as they were sequentially tested in the trial (100×10⁶ CAR+ T cells [one or two doses], 200×10⁶ CAR+ T cells [one or two doses]). Leukapheresed patients could receive bridging chemotherapy based on investigator assessment of disease burden and tumor progression risk. Lymphodepleting (LD) chemotherapy was administered over 3 days, including fludarabine (30 mg/m2 i.v. daily) and cyclophosphamide (300 mg/m 2 i.v. daily), followed 2 days later by intravenous infusion of IM19 at the assigned dose. The first three subjects in each dose group will receive the second LD chemotherapy and infusion of IM19 CAR-T cells for consolidation treatment (with the same dosage as the first treatment) if the efficacy evaluation after the first infusion shows no progression and no DLT occurs. The investigators can determine the start time of consolidation treatment based on the patient's tolerance, but no later than 60 days after the first infusion. Efficacy was assessed at 1, 3, 9, 12, 18, and 24 months post first infusion. Safety events were monitored from beginning of LD through 2 years follow-up. The primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate. Results: Between Mar 3, 2022, and May 5, 2023, Five patients underwent leukapheresis for manufacture of CAR+ T cells (IM19) and all received bridging chemotherapy during the production of IM19. ALL 5 patients received LD and first infusion of IM19 at a dose of 100*10^6 CAR+ cells and no DLTs were observed. CRS was reported only in 1 patient(grade 1) and no patients developed ICANS. ALL 5 patients achieved CR on 28 days after first infusion. The median maximum CAR-T cells expansion (Cmax) was 156×10⁶ CAR+ cells/L, and median area under the curve from 0-28 days post-first infusion (AUC0-28d) was 860 day×CAR+ cells/L. 2 patients received the second LD chemotherapy and infusion of IM19 CAR-T cells for consolidation treatment (with the same dosage as the first treatment) at 44th days post first infusion. No DLTs，CRS or ICANS were observed after second infusion. Meanwhile, CAR-T cells can not be detected at 1, 4, 7, 10, 14, 21 and 28 days post second infusion by Flow cytometry in 2 patients. One patient maintained complete remission after 9 months of follow-up and another patient experience PD at 7th month after first infusion. For three patients who received single infusion of IM19, one maintained complete remission after 6 months of follow-up，one progressed at 3th month after infusion and one are still waiting for second efficacy evaluation. Conclusions: Initial data from this Phase I study demonstrate that use of IM19 resulted in a high objective response rate, with a low incidence of grade 3 or worse cytokine release syndrome and neurological events in patients with relapsed or refractory MCL. We observed that CAR-T cells cannot expand in vivo after secondary infusion. Therefore, secondary infusion may not be necessary.