TNFRSF8 expression

P1/2, N=38, Active, not recruiting, UNC Lineberger Comprehensive Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Aug 2038 --> Nov 2039 | Trial primary completion date: Sep 2027 --> Dec 2025

The antibody-drug conjugate brentuximab vedotin (BV) has significantly improved outcomes for CD30-expressing lymphomas. The ECHELON-2 trial established BV combined with cyclophosphamide, doxorubicin, and prednisone (CHP) as a frontline standard for systemic anaplastic large cell lymphoma, demonstrating superior survival over the traditional CHOP regimen...We assess alternative strategies, such as BV-based combinations with immunotherapies or alternative chemotherapies, the integration of other targeted agents, and the transformative potential of advanced cellular treatments like anti-CD30 chimeric antigen receptor (CAR)-T cell therapy for relapsed/refractory disease. The collective evidence signals a paradigm shift from a one-size-fits-all approach toward personalized, precision-driven strategies aimed at maximizing efficacy, minimizing toxicity, and improving long-term quality of life for patients with CD30-positive lymphomas.

GI mastocytosis is highly predictive of SM in BM; however, most SM-BM+ patients are SM-GI-. The SM-BM- patients are very unlikely to be SM-GI+. Because GI neoplastic mast cells are often tryptase negative, diagnostic evaluation should include CD117 and CD25 immunohistochemistry, as well as KIT D816V mutation analysis by ddPCR as needed.

EBV infection appears to influence disease progression and prognosis in EBER-positive patients, whereas EBER-negative cases more closely align with the disease characteristics observed in other peripheral T-cell lymphomas. The results suggest that stratifying patients by EBV status is crucial for optimizing AITL clinical management.

This case highlights the diagnostic challenge posed by rare penile lesions and, more importantly, the therapeutic dilemma of selecting an appropriate treatment for a disease that is localized yet multifocal. The successful outcome with systemic brentuximab vedotin plus cyclophosphamide, doxorubicin, vincristine, and prednisone therapy, a deviation from standard guidelines for unifocal primary cutaneous anaplastic large cell lymphoma, underscores the need for individualized treatment strategies and further research to establish risk-adapted guidelines for this rare clinical entity.

Reversal experiments demonstrated that NF-κB pathway inhibitors can reverse the effector function of CAIX.CD30(ICD) CAR-T cells, while CAIX-IKKβ CAR-T cells with self-activated NF-κB pathway also exhibit significant functional advantages. By integrating autonomous costimulatory signaling, we demonstrated improved CAR-T cell persistence, proliferation, and antitumor activity across multiple preclinical models, highlighting the therapeutic potential of this approach for both hematologic malignancies and solid tumors.

Importantly, pharmacologic inhibition of IL-1R signaling significantly enhances the antitumor activity of CD30-specific CAR therapies both in vitro and in ALCL xenograft models. Collectively, our findings uncover a novel mechanism of immune resistance and nominate IL-1R blockade as a promising combinatorial strategy to improve CAR-based immunotherapy in ALCL.

This is a unique presentation of LyP with concurrent DUSP22-IRF4 gene rearrangement and TCR gamma-delta phenotype along with an indolent clinical course. Diagnosing LyP can be particularly challenging due to its histologic similarities with other cutaneous lymphomas, underscoring the importance of distinguishing this relatively benign condition from more aggressive malignancies.

We describe the road to the discovery of the CD30 molecule and the way CD30 has contributed to more precise diagnosis and classification of lymphomas. Moreover, we address how anti-CD30 immunotherapy was developed and the impact of the anti-CD30-auristatin conjugate and anti-CD30 CAR-T cells in treating CD30-expressing lymphomas.

This case highlights the diagnostic value of effusion cytology combined with cell block immunocytochemistry in establishing a definitive diagnosis of ALCL from pleural fluid, even in the absence of an overt mass lesion. Early recognition of this rare presentation is critical for timely management, as effusion-dominant ALCL may portend an aggressive clinical course.

Among 11 patients who underwent allogeneic stem cell transplantation, two developed acute graft-versus-host disease; median PFS was 234 days (95% CI 168-343), compared with 180 days (95% CI 96-279) without transplantation. BV-CHP demonstrated high ORR and CRR across age groups and ATL subtypes with a manageable safety profile, supporting its potential use as a standard treatment option.

P2, N=78, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jan 2026 --> Apr 2026