Mantle Cell Lymphoma

Anlotinib effectively inhibits proliferation and induces apoptosis in MCL both in vitro and in vivo. This inhibition is likely linked to suppressing phosphorylation in the PI3K/Akt/mTOR pathway.

This review provides a comprehensive overview of the available data on LINK-A, focusing on its molecular regulatory pathways and clinical significance. By exploring the multifaceted nature of LINK-A in cancer, the review aims to offer a valuable resource for future research directions, potentially guiding the development of novel therapeutic strategies targeting this lncRNA in cancer treatment.

MNDA was highly expressed in MZL with a potential utility in differential diagnosis between MZL and RLH as well as FL, whereas its value in distinguishing MZL from MCL, CLL/SLL is limited. In addition, MNDA expression in DLBCL was more frequently seen in the non-GCB group and the BCL2/MYC double-expression group, and demonstrated a correlation with CD5, which deserves further investigation. The clinical relevance of MNDA and its correlation with the prognosis of these lymphomas also warrant to be fully elucidated.

This review synthesizes current knowledge on genetic mutations in MCL and their impact on prognosis. It aims to explore the prognostic value of genetic markers related to population traits, emphasizing the importance of tailored molecular medicine in MCL.

Among possible determinants of CD4+ T cell recovery, we recognized infusion of a 4-1BB product (tisagenlecleucel, TSA) in comparison with a CD28 (axicabtagene/brexucabtagene, AXI/BRX) (hazard ratio [HR] [95% CI]: 5.79 [1.16-24.12] p = 0.016). We conclude that a faster CAR- CD4+ T cell recovery is associated with TSA as compared to AXI/BRX. Month-1 CAR- CD4+ T cell subset recovery could represent a "red flag" for CAR-T cell therapy failure in DLBCL patients.

P2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=50 --> 32

P2, N=40, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

P=N/A, N=10, Recruiting, Massachusetts General Hospital | Not yet recruiting --> Recruiting

Here we demonstrate that EBV- BL comprises two subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

P2, N=15, Completed, SCRI Development Innovations, LLC | Active, not recruiting --> Completed | Trial completion date: Aug 2027 --> Apr 2024 | Trial primary completion date: Aug 2027 --> Apr 2024

Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.

The covalently bound Ibrutinib molecule, recognized for its ability to inhibit BTK, was used as the query molecule...Covalent docking simulations were applied to the selected small-molecules obtained through text mining from databases. Potent hit molecules capable of inhibiting BTKs through virtual screening algorithms were identified, paving the way for novel therapeutic strategies in the treatment of CLL.

P2, N=25, Active, not recruiting, Polish Lymphoma Research Group | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Jun 2024

P3, N=490, Not yet recruiting, InnoCare Pharma Inc.

P2, N=20, Active, not recruiting, University of Washington | Trial completion date: Aug 2028 --> Aug 2029 | Trial primary completion date: Apr 2024 --> Apr 2025

P=N/A, N=229, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Mar 2024 | Trial primary completion date: Jun 2024 --> Mar 2024

P1, N=78, Recruiting, Adicet Bio, Inc | Trial completion date: Mar 2024 --> Dec 2027 | Trial primary completion date: Mar 2023 --> Dec 2025

P1/2, N=27, Not yet recruiting, OHSU Knight Cancer Institute

SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

P2, N=40, Not yet recruiting, City of Hope Medical Center | Initiation date: Mar 2024 --> Jun 2024

Immunomodulatory drugs like lenalidomide reduce the levels of MCL-associated CD163+ macrophages and enhance macrophage phagocytic activity. Similarly, clinical approaches targeting the CD47 "don't eat me" signalling, in combination with the anti-CD20-antibody rituximab, demonstrate increased macrophage activity and phagocytosis of MCL tumour cells. Cell-based therapies such as chimeric antigen receptor (CAR) T-cell have shown promise but various challenges persist, leading to a potential interest in CAR-macrophages (CAR-M). When macrophages are recruited to the TME, they offer advantages including phagocytic function and responsiveness to microenvironment alterations, suggesting their potential as a manipulable and inducible alternative when CAR T-cell therapies fails in the complex landscape of MCL treatment.

P1, N=100, Recruiting, Poseida Therapeutics, Inc. | Initiation date: Jan 2024 --> Apr 2024

P1/2, N=466, Recruiting, BeiGene | N=291 --> 466

P1, N=120, Recruiting, Stanford University | Not yet recruiting --> Recruiting

P2, N=52, Recruiting, Fudan University

P1, N=36, Not yet recruiting, Roswell Park Cancer Institute

P1, N=120, Not yet recruiting, Stanford University

Targeting DNMT3A with low-dose decitabine inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting DNMT3A-mediated metabolic reprogramming to OXPHOS with decitabine provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory MCL.

We then place the tumor in its complex ecosystem to decipher the dialog with the multiple TME components and show how the resulting protumoral signals could be disrupted with innovative therapeutics strategies. Finally, we discuss how these progresses could be integrated in a personalized approach in MCL.

P1, N=16, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=36, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Jan 2025 --> Sep 2024

Our data strongly support investigation of the chemotherapy-free palbociclib and venetoclax combination as an innovative treatment strategy for post-ibrutinib MCL patients without RB1 deletion.

P1/2, N=860, Active, not recruiting, Loxo Oncology, Inc. | Trial completion date: Apr 2024 --> Jan 2028 | Trial primary completion date: Apr 2024 --> Sep 2027

P1, N=40, Recruiting, Novartis Pharmaceuticals | N=124 --> 40 | Trial completion date: Jun 2027 --> Oct 2026 | Trial primary completion date: Jun 2027 --> Oct 2026

Time-to-event analyses showed that MCL international prognostic index (MIPI) high-risk category and higher STAT5 response were predictors of shorter PFS and OS whilst MIPI high-risk category and high SYK response predicted shorter OS. In conclusion, we identified BCR signaling properties associated with poor clinical outcome and resistance to ibrutinib, thus highlighting the prognostic and predictive significance of BCR activity and advancing our understanding of signaling heterogeneity underlying clinical behavior of MCL.

P1, N=10, Terminated, Amgen | Completed --> Terminated; Amgen decided to discontinue study because of a business decision and not because of safety reasons

P2, N=10, Not yet recruiting, Dalian Medical University

P1, N=27, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

P1, N=150, Recruiting, Nkarta Inc. | Trial primary completion date: Dec 2023 --> Aug 2024

P1/2, N=69, Recruiting, Barbara Ann Karmanos Cancer Institute | Phase classification: P1b/2 --> P1/2 | N=44 --> 69 | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=49, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Aug 2024 --> Jun 2026 | Trial primary completion date: Aug 2024 --> Jun 2025

P2, N=23, Active, not recruiting, Emory University | Trial primary completion date: Sep 2023 --> Sep 2024