Diffuse Large B Cell Lymphoma

P2, N=20, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

We also demonstrated that, compared with that with each drug used as single agents, the combined 5-aza and HDAC3i treatment induced the epigenetic remodeling of DLBCL cells, which resulted in a more potent reexpression of differentiation genes, including XBP1 and ATF4. Our results highlight the importance of specifically targeting multiple layers of the epigenome to maximize the efficacy of epigenetic-based therapies.

Expression of IRTA1 alone, or either IRTA1+ or MNDA+, was less frequent among MZL with plasma cell differentiation than among MZL with classical cell morphology (p=0.063 and 0.071, respectively), albeit not significantly. IRTA1 and MNDA are sensitive and specific markers for the differential diagnosis of MZL, and they may be helpful in distinguishing MZL from histologic mimics.

P3, N=239, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Dec 2026 --> Jan 2026

P2, N=30, Active, not recruiting, Sun Yat-sen University

P1, N=18, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

In the near future, the predictive value of ABC/GCB classification is expected to increase in relation to novel targeted therapeutic regimens. Integration of transcriptomic and genetic data will be essential for independent and individualized risk assessment in the molecular diagnostics of DLBCL.

Notably, combined treatment with the PRMT5 inhibitor GSK3326595 and DMF synergistically enhances anti-tumor activity in a patient-derived xenograft (PDX) model. These findings reveal a previously unrecognized PRMT5-ATF5-SLC7A11 axis that drives ferroptosis resistance in B-cell lymphomas and provide a strong rationale for targeting PRMT5 to potentiate ferroptosis-based therapies in relapsed or refractory disease.

For in vivo validation, a murine lymphoma model was treated with nicotinamide riboside (NR), and tumor-infiltrating NK cell function and lipid accumulation were analyzed...CD36-driven lipid metabolic disruption leads to NK cell dysfunction and ferroptosis in DLBCL. Thus, restoration of NAD+ levels represents a promising therapeutic strategy to enhance NK cell effector function and improve antitumor immunity in DLBCL.

Together, our data indicate that ZDHHC11 promotes BL cell growth at least in part by stimulating expression of MEF2B, which promoted BL cell survival through both BCL6-dependent and independent pathways. Our work highlighted the importance of the MEF2B-BCL6 axis, which strongly supports BL growth and identified ZDHHC11 as a novel regulator of this axis.

Importantly, our AI-aided approach not only identified this axis but also predicted its vulnerability to metabolic intervention: both methotrexate treatment and LDHA knockdown restored metabolic balance, reversed T‑cell exhaustion, and suppressed tumor growth. These findings highlight the power of ML in uncovering multi-targetable metabolic-immune networks and in guiding therapeutic strategies to overcome immune evasion in DLBCL.

Even in the era of rituximab-based immunochemotherapy, survival benefits for these patients remain limited. In recent years, with the development of precision assessment tools such as genotyping and advances in research on personalized immunotargeted therapies, the understanding of CD5(+) DLBCL has deepened, offering the prospect of improved treatment outcomes for some patients. To further standardize diagnosis and treatment practices, the Lymphoid Disease Group, Chinese Society of Hematology, Chinese Medical Association and the Lymphoma Expert Committee of China Anti-Cancer Association have organized relevant experts to formulate this consensus, aiming to guide the standardized diagnosis and treatment of CD5(+) DLBCL patients in China.