Marginal Zone Lymphoma

P1, N=18, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not due to any safety or tolerability concerns.

P=N/A, N=28, Not yet recruiting, Army Medical Center of PLA; Army Medical Center of PLA

P2, N=25, Not yet recruiting, University of California, Davis

SMZL, when requiring therapy, are treated with splenectomy ore more frequently monotherapy Rituximab or immunochemotherapy depending on age, comorbidities and tumor burden. Conventional treatments may be a suitable option but novel therapies are more frequently used. In this review, we focus on the role of Bruton Tyrosine Kinases (where only Zanubrutinib has marketing authorization in France), PI3Kinases, Syk and BCL-2 inhibitors as well as on the results of immunomodulatory drugs and more recently the use of bispecific antibodies and T-cell chimeric antigen receptor (CAR-T cell).

P2, N=49, Recruiting, Emory University | Trial primary completion date: Jan 2025 --> Sep 2025

P2, N=120, Active, not recruiting, Cellectar Biosciences, Inc. | Trial primary completion date: Dec 2024 --> Dec 2025

NGS enhances the diagnostic accuracy of mature B-cell lymphomas by complementing traditional methods, refining WHO-classified subtypes, and improving detection in cases with inconclusive cytogenetics or morphology. NGS may reduce the need for unnecessary bone marrow re-punctures by providing additional information in ambiguous cases.

P1, N=42, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting

Selection of patients who might benefit with CNS prophylactic agents is of utmost importance. On the whole, most cases of high grade cutaneous DLBCLs need to have CNS chemo-prophylaxis.

CYLD loss was sufficient to induce BcR signaling, conferring increased resistance to ibrutinib treatment in vitro. In summary, our work uncovers a novel role of CYLD as a key regulator in SMZL pathogenesis, dissemination, and resistance to targeted agents. On these grounds, CYLD could be proposed as a novel target for patient stratification and personalized interventions.

Significant features evident in both HRCT imaging and pathological analysis were identified in pulmonary MALT lymphoma cases. These findings are anticipated to play a crucial role in facilitating early diagnosis and determining optimal treatment strategies.

Our results reveal the cellular composition, key pathways, and critical immune microenvironment implicated in the development of these two diseases. These findings provide important insights into the pathogenesis of these two diseases and highlight the differences between them.

P2, N=36, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P2, N=135, Completed, Fred Hutchinson Cancer Center | Active, not recruiting --> Completed

P=N/A, N=40, Not yet recruiting, UNC Lineberger Comprehensive Cancer Center

P1, N=22, Active, not recruiting, Beth Christian | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Dec 2024 --> Aug 2025

This overexpression may facilitate the enrichment of CD138+ plasma cells and is associated with elevated serum IgG4 levels in patients with IgG4-ROD. Additionally, it may promote the proliferation of CD20+ B lymphocytes in patients with MALT lymphoma.APRIL may play a certain role in the possible transformation of IgG4-ROD into MALT lymphoma.

P1, N=37, Not yet recruiting, City of Hope Medical Center

P1/2, N=666, Active, not recruiting, Genmab | Trial primary completion date: Mar 2025 --> Apr 2026

P1, N=48, Active, not recruiting, Kami Maddocks, MD | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Mar 2014 --> May 2025

P1, N=200, Recruiting, ADC Therapeutics S.A. | Trial completion date: Feb 2026 --> Dec 2026 | Trial primary completion date: Feb 2025 --> Dec 2025

This Perspective provides an overview of MALT1's structural and functional characteristics, summarizes recent advancements in small-molecule inhibitors and degraders targeting this protein, and discusses compound structures, structure-activity relationship (SAR) analyses, and biological activities. We aim to inform future research efforts to enhance the activity, selectivity, and pharmacological properties of MALT1-targeting compounds, establishing a foundational framework for drug development in this critical area of cancer therapy.

P1, N=30, Active, not recruiting, Bio-Path Holdings, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> Apr 2025 | Trial primary completion date: Sep 2024 --> Apr 2025

Interference with AjMALT1 also led to downregulation of AjTRAF6 and AjRel expression, as well as inhibited nuclear translocation of AjRel. These findings suggest AjMALT1 exacerbates intestinal and coelomic inflammation by activating the AjTRAF6-dependent NF-κB pathway in A. japonicus.

P1/2, N=127, Recruiting, BeiGene | Trial completion date: Mar 2027 --> Sep 2027 | Trial primary completion date: Mar 2027 --> Feb 2026

P1, N=12, Recruiting, Medical College of Wisconsin | Not yet recruiting --> Recruiting

P1/2, N=100, Recruiting, Medical College of Wisconsin | Trial completion date: Jan 2025 --> Jun 2028 | Trial primary completion date: Jan 2025 --> Jun 2026

P=N/A, N=59, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Finally, the genesis of salivary gland EMZL may be closely associated with GPR34 activation that is caused by mutation/t(X;14)(p11;q32) and/or paracrine stimulation mediated by ligand generated by lymphoepithelial lesions. This review will focus on these novel molecular insights and how these advances may provide a paradigm for future investigations.

P1, N=37, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

P=N/A, N=160, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P2, N=300, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Nov 2025 --> Jun 2026 | Trial primary completion date: Jan 2025 --> Jun 2025

P2, N=23, Recruiting, University of Utah | Not yet recruiting --> Recruiting

Trial Registration: ClinicalTrials.gov. (www.clinicaltrials.gov, NCT06086327).

P2, N=44, Completed, International Extranodal Lymphoma Study Group (IELSG) | Active, not recruiting --> Completed | Trial completion date: Nov 2029 --> Dec 2024

P1, N=27, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jul 2025 | Trial primary completion date: Dec 2024 --> Jul 2025

P1, N=18, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2024 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P2, N=25, Not yet recruiting, Izidore Lossos, MD

P1/2, N=621, Recruiting, BeiGene | Trial completion date: Mar 2028 --> Dec 2028 | Trial primary completion date: Mar 2025 --> Dec 2025

P2, N=65, Not yet recruiting, Masonic Cancer Center, University of Minnesota

P2, N=145, Not yet recruiting, Ruijin Hospital

Citrus analysis showed a significant increase in the CD16+ CD4+ and CD16+ CD8+ T cell populations in the COP group compared to lung malignancies. Our findings reveal distinct T cell immunophenotypes in COP versus lung malignancies, particularly increased CD16+ T cells in COP, which could serve as potential diagnostic biomarkers.