TNFRSF8 positive

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.

Under aptamer guidance, multivalent aptamer oligonucleotide complex NK cells specifically bind to CD30-positive lymphoma cells and trigger more effective antitumor effects than that of parental NK cells, both in vitro and in vivo. Therefore, the proposed approach endows NK cells with tumor-specific targeting ability and enhances their adoptive therapeutic efficiency in CD30-positive lymphoma, showing substantial potential for application in the clinical treatment of malignant lymphoma.

This case series found that JAK2 fusions were seen in aggressive cytotoxic CTCL as well as in T-cell lymphomas with more indolent behavior, possibly representing a precursor lesion to aggressive evolution with age and comorbidities. The prominence of these fusions supports a potentially larger role for JAK2 targeting in patients with early-stage MF, CD30-positive LPD, or overlap presentations.

This case highlights bexarotene as a promising therapeutic option for refractory pcALCL. Our experience reinforces the potential of bexarotene as a viable treatment for pcALCL, particularly in recurrent or refractory cases where conventional therapies are contraindicated or ineffective.

P2, N=48, Active, not recruiting, City of Hope Medical Center | Trial completion date: Aug 2025 --> Jul 2026

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.

In phase I of this trial, we could show that BV can safely be added to BeEAM-HDCT (bendamustine, etoposide, cytarabine and melphalan). In conclusion, adding BV to BeEAM does not improve outcomes after HDCT, and may increase pulmonary toxicity. Frequent prior exposure to BV may have limited the potential benefit of the combination.

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.

IN-SCT is a diagnostically challenging tumor characterized by the triad of inflammatory stroma, EWSR1::ATF1 fusion, and aggressive clinical behavior. Accurate recognition of its unique features supports its classification as a distinct entity. Surgical excision followed by adjuvant chemotherapy may benefit patients with advanced disease. The distinct molecular profile of IN-SCT may provide future directions for targeted therapy and diagnostic refinement.

Bone marrow biopsy revealed lymphoma infiltration, prompting initiation of A+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) chemotherapy for stage IV disease based on Karnofsky Performance Status...Treatment depends on disease stage, with early stage managed by ABVD (Adriamycin, Bleomycin sulfate, Vinblastine sulfate, Dacarbazine) chemotherapy and radiation, while advanced cases require extended A+AVD chemotherapy. PPL accounts for <2% of extra-nodal lymphomas but remains a potentially treatable entity. This case underscores the importance of obtaining tissue diagnosis in the setting of a pancreatic mass before embarking on definitive treatment.

Upfront autologous stem cell transplantation is currently controversial, and ongoing randomized controlled trials are expected to clarify its role. With advances in our understanding of the molecular and genetic characteristics of PTCL and potential predictive biomarkers, the future development of treatment will focus on more stratified approaches, and ongoing trials are expected to provide further insights into optimizing these treatment strategies.

P1/2, N=45, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | N=30 --> 45 | Trial completion date: Apr 2027 --> Sep 2025 | Trial primary completion date: Apr 2027 --> Sep 2025