Diffuse Large B Cell Lymphoma

P2, N=59, Active, not recruiting, Dizal Pharmaceuticals | Recruiting --> Active, not recruiting | N=180 --> 59 | Trial completion date: Apr 2028 --> Aug 2026 | Trial primary completion date: Oct 2027 --> Jan 2026

BsAbs such as epcoritamab, glofitamab, and mosunetuzumab have demonstrated substantial efficacy across both aggressive and indolent B-cell non-Hodgkin lymphomas (B-NHL), with largely manageable safety profiles...Approaches incorporating BsAbs into cytotoxic backbones and antibody-drug conjugates, as well as chemotherapy-free regimens such as BsAbs combined with lenalidomide, are discussed...BsAbs represent a major advance in B-NHL, offering high rates of deep remission with predictable safety and outpatient feasibility. As trial data continues to mature, BsAb-based regimens are poised to become foundational across multiple lines of therapy, reshaping expectations for patients with both aggressive and indolent lymphomas.

Although the R-CHOP regimen effectively cures 60-70% of patients, 30-40% of patients relapse or develop resistance, highlighting the need for new biomarkers to improve prognosis and therapeutic strategies...Our findings suggest that the SREBF2-ACOT7 axis plays a critical role in DLBCL by promoting tumor cell growth, invasion, and survival. ACOT7 could serve as a potential prognostic biomarker and therapeutic target for DLBCL, providing new insights into the molecular mechanisms of this aggressive lymphoma.

In patients with Richter transformation, epcoritamab monotherapy showed clinically meaningful antitumour activity, although the investigator-assessed overall response rate was below the alternative hypothesis of 50%, with a safety profile consistent with previous studies. These findings support further investigation of epcoritamab as a potential treatment option for patients with Richter transformation.

Comparative insights highlight the advantages of liso-cel over other CAR-T cell products, such as axicabtagene ciloleucel and tisagenlecleucel in terms of toxicity, logistics, and outpatient feasibility. With ongoing improvements in manufacturing, accessibility, and biomarker development, liso-cel is well-positioned to become a central component in the evolving treatment paradigm for FL. However, challenges remain regarding durability of response, cost, and access, which warrant careful discussion.

The patient was given R-CHOP chemotherapy and intrathecal methotrexate with a favorable early response...Image-guided biopsy and immunophenotyping at an early stage are crucial to avoid misdiagnosis and guide appropriate therapy. Individualized and risk-adapted approaches are crucial in maximizing the outcome in such aggressive and rare presentations.

Mechanistically, we show that 1α,25(OH) 2D 3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH) 2D 3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.

ACC and DLBC shared a consensus expression program, whereas STAD diverged; chromatin analysis showed AP-2 motifs near microbe-responsive genes in ACC and DLBC but not STAD, supporting cohort-specific regulation. Collectively, AP-2 family members emerge as plausible mediators of tumor microbiota-host interplay, warranting further mechanistic and translational research.

Interestingly, measuring intratumoral FAP levels revealed an inverse pattern, with diffuse large B-cell lymphoma showing higher tissue FAP localization compared with follicular lymphoma (p < 0.001). These findings provide new insights into the biological and clinical significance of FAP in lymphoid malignancies, particularly highlighting the importance of sFAP activity as a potential prognostic marker in aggressive lymphoid malignancies.

Moreover, these groups were identified using surrogate immunohistochemical markers: EBNA2, PDL1, and IDO1. In conclusion, the molecular studies assessing tumor-host interaction enhances understanding of the EBV+ large B-cell lymphoma spectrum and benefits pathological diagnosis and clinical management.

P=N/A, N=179, Recruiting, Novartis Pharmaceuticals | N=500 --> 179

This study demonstrated a causal effect of CTSS on DLBCL based on the MR algorithm. Follow-up studies are needed to elucidate the underlying mechanisms between them and explore promising new therapeutic options for DLBCL patients.