Diffuse Large B Cell Lymphoma

P2, N=50, Recruiting, Memorial Sloan Kettering Cancer Center

This approach can improve the ORR and does not increase the incidence of CRS and ICANS. The mechanism may be related to the regulation of T-cell co-stimulatory molecules, which demands further exploration.

In the first part of the paper, we review the following categories: LBLs transformed from indolent B-cell lymphomas, diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), double-hit/triple-hit lymphomas (DH/TH), high-grade large B-cell lymphoma, not otherwise specified (HGBCL, NOS), LBCL with IRF4 rearrangement, Burkitt lymphoma (BL) and HGBCL/LBCL with 11q aberration, focusing on the differences between the two classifications. In the second part of the paper, we provide a practical diagnostic algorithm when facing LBCLs in routine daily practice.

Furthermore, patients over 60 years old and those with a higher Revised International Prognostic Index (R-IPI) had significantly higher CD79b expression, both of which are associated with a significant benefit from adding an anti-CD79b drug conjugate to first-line chemotherapy in diffuse large B-cell lymphomas. In conclusion, the quantitative flow cytometric analysis of CD79b surface expression in aggressive B-cell lymphomas provides clinically relevant information, highlighting its potential usefulness in guiding therapeutic decisions.

The combined workflow predicted selective responses to BCL2 inhibition (venetoclax) and non-canonical NF-κB inhibition (Amgen16)...Combined molecular fingerprinting and computational modelling provides a strategy for the precision use of BH3-mimetics and NF-κB inhibitors in DLBCL. TME-mimicking co-culture provides resistance to BH3-mimetics through BCLXL, which can be overcome by inhibition of non-canonical NF-κB.Multidisciplinary profiling reveals how high NF-κB activity leads to crosstalk, and BH3-mimetic resistance counteracted by BTK inhibition.

P=N/A, N=100, Active, not recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P2, N=76, Active, not recruiting, Seoul National University Hospital | Recruiting --> Active, not recruiting

P=N/A, N=750, Not yet recruiting, University of Nottingham

P1, N=23, Not yet recruiting, City of Hope Medical Center

P1/2, N=38, Completed, Prof. Dr. Clemens Schmitt | Active, not recruiting --> Completed | Trial primary completion date: Jun 2024 --> Nov 2024

No abstract available

P2, N=27, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2025 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Apr 2025

A high amount of CD163+ TAM interactions with distinct TILs translated to unfavorable survival both in GCB DLBCL and T-DLBCL, whereas a high number of interactions between TILs and TAMs, CD4+ TILs and TAMs, and CD4+ TILs and other TILs associated with favorable outcomes only in T-DLBCL. Together, our data demonstrate biologically and clinically relevant differences in the composition of and cellular interactions in the TME between various DLBCL entities.

In addition, THL attenuated DOX-induced myocardial hypertrophy and cardiac fibrosis in mice, in conjunction with attenuation of DOX-induced upregulation of C-caspase3, Bax, NLRP3, C-caspase-1/Pro-caspase, GSDMD-N/GSDMD, IL-1β, and IL-18 in heart or serum samples. In conclusion, our data supported that THL alleviates the cardiotoxic effects of DOX and suppresses NLRP3 inflammasome in the mouse model, suggesting that THL as a potential drug for DOXIC.

No abstract available

Indeed, no structural variations or copy number alterations involving PD-1 ligands were detected by targeted-capture sequencing and fluorescence in situ hybridization. While further studies are warranted, we may have confirmed similarity between PCNS-LBCLs and intravascular large B-cell lymphomas from a molecular standpoint.

P1/2, N=543, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting

P1, N=54, Recruiting, Roswell Park Cancer Institute | N=36 --> 54

Although CL is thought to be a distinct subtype of PCNSL, our case demonstrates that PCNSL may develop on a background of diffuse CL. In patients with subacute neurologic decline and MRI findings of diffuse leukoencephalopathy, diffuse CL should be considered.

P1, N=7, Completed, Kymera Therapeutics, Inc. | Suspended --> Completed | N=80 --> 7

P2, N=20, Recruiting, University Medical Center Groningen | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: May 2024 --> Apr 2025

P=N/A, N=6, Active, not recruiting, University College, London | Trial completion date: May 2024 --> Jun 2025

P1, N=106, Recruiting, Umoja Biopharma | Not yet recruiting --> Recruiting

P1/2, N=11, Completed, Mayo Clinic | Active, not recruiting --> Completed

P1, N=3, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jan 2026 --> Mar 2025

High-throughput sequencing identified EWSR1::CREM fusion in case 1, whereas fluorescence in situ hybridization detected EWSR1::CREB1 fusion in case 2. These cases expand the morphological and immunophenotypic characteristics of malignant epithelioid tumors with EWSR1::CREB fusion, highlighting the diagnostic challenges of immunohistochemistry and value of molecular testing for accurate diagnosis.

CONCLUSIONS Mediastinal DLBCL infiltrating the myocardium is aggressive and presents a treatment dilemma, as retreat of the mass from emergency chemotherapy can result in catastrophic complications. Our patient's condition, rarely described in literature, was severe blood flow obstruction and significant arrhythmia, both of which improved after only 1 cycle of chemotherapy and without need for permanent pacemaker.

Therefore, EZH2 inhibition enhances CAR-T cell efficacy through direct effects on CAR-T cells, in addition to rendering lymphoma B cells immunogenic. This approach is currently being evaluated in two clinical trials, NCT05934838 and NCT05994235, to improve immunotherapy outcomes in B cell lymphoma patients.

Treatment included R-CHOP (n=26), R-DA EPOCH (n=2), MTR (n=1), and R-MPV (n=1).26.66% had PD-L1 <1% while 73.33% had PD-L1 ≥1%; 33.33% had PD-L1 <5%, while 66.67% had PD-L1 ≥5%...Limitations include small number of patients, short follow up and inclusion of 2 patients of primary CNS lymphoma, that might have affected the analysis minimally. Further research is essential to standardize the cutoff value and scoring method.

Base substitution or indel variants were detected in TP53 (28% of cases), KMT2D (25%), CREBBP (14%), EZH2 (8%), MYD88 (8%), TNFRSF14 (8%), ATM (8%), NOTCH1 (7%), ARID1A (6%), B2M (6%), TNFAIP3 (6%), PIM1 (4%), CD79B (3%), BTK (2%, 97% of which were C481X ibrutinib resistance mutations in cases of CLL), MEF2B (2%), BCL2 (1%), and PLCG2 (1%)...Overall, 75% of FLs harbored a canonical IGH : : BCL2 rearrangement and 86% of MCLs harbored a canonical IGH : : CCND1 rearrangement.Conclusions : This analysis of 3,692 samples demonstrated that the F1H assay platform reliably detects a broad landscape of genomic alterations across a range of mature B-cell lymphoma/leukemia subtypes. By detecting all classes of genomic alterations in a single sequencing reaction, F1H provides an important advantage over single-gene and small-panel molecular tests in an era when the diagnosis, prognosis, and treatment of hematological malignancies increasingly rely on assessing the presence, as well as the absence, of numerous genomic alterations.

While 12-month PFS failed to reach statistical significance, subgroup analyses favor Pola-R-CHP. Further research with a wider population, longer follow-up, and screening of advantageous groups are warranted.

This is an analysis of 127 patients with HIV with Burkitt lymphoma (HIV-BL) and diffuse large B-cell lymphoma (HIV-DLBCL) treated at the Zhongnan Hospital of Wuhan University over a 17-year period during the ART and rituximab era...Current China practice favours the treatment of HIV-BL and HIV-DLBCL similarly to the HIV-negative population with the use of concurrent ART. However, due to the extremely low percentage of patients receiving ART prior to the lymphoma diagnosis, the high percentage of patients with poor performance status, and the advanced stage at diagnosis, the treatment of HIV-related lymphoma remains the major challenge in China.

Seven months later, the patient underwent follow-up EGD, and the disappearance of lymphoma cells was confirmed histopathologically by biopsy. Repeated and detailed endoscopic examination should be considered in an immunosuppressed patient with treatment-resistant gastric or duodenal ulcers.

P2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2027

P1, N=3, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=88 --> 3

This association will assist in identifying a target population that may benefit from MYD88-specific treatment regimens. This may exponentially improve the outcome of patients with DLBCL harboring this mutation.

Consistently, in vivo experiments demonstrated that the CD4+CD25+ Treg population dampened the antitumor activity of CD8+CAR-T cells, while depletion of Tregs from CD4+CAR-T cells enhanced the tumoricidal effect. These findings emphasize the potential role of CAR Treg cells in therapeutic resistance, suggesting that the depletion of Tregs in the anti-CD19 CAR-T population may serve as a strategy to augment the anticancer effect of CD8+CAR-T cells.

P2, N=65, Active, not recruiting, University of Southampton | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Oct 2024 --> May 2026

The mitotic index (HR: 1.03, CI 0.9-1.19, p = 0.645), Ki-67 (HR: 1.00, CI 0.98-1.02, p = 0.845) and > 30% of tumour-infiltrating T cells (HR: 0.38, CI 0.09-1.56, p = 0.175) were not significantly associated with PFS. In this uniformly RT treated population of FeNL, none of the evaluated pre-RT histologic parameters could predict early treatment failure.

P3, N=1046, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=423, Active, not recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Mar 2025 --> Jun 2025

P3, N=700, Recruiting, Janssen Research & Development, LLC | Enrolling by invitation --> Recruiting