CD30 is overexpressed in many T-cell lymphoma (TCL) entities, including subsets of peripheral T-cell lymphomas (PTCL) and cutaneous T-cell lymphomas (CTCL). The antibody–drug conjugate brentuximab vedotin (BV), targeting CD30-positive cells, has been approved for the treatment of relapsed or refractory (R/R) systemic anaplastic large cell lymphoma (sALCL), and primary cutaneous anaplastic large cell lymphoma or mycosis fungoides in patients who have received previous systemic therapy. However, many patients still experience disease progression after BV monotherapy. Extensive efforts have been dedicated to investigating effective combinations of BV. A phase III clinical study demonstrated that the combination of BV with cyclophosphamide, doxorubicin, and prednisone (CHP) is superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for CD30-positive PTCL. This study led to the approval of BV with CHP as the first-line therapy for CD30-positive PTCL (sALCL in Europe). We summarize the encouraging combination applications of BV in this review. Ongoing studies on combination therapies of BV are also listed, highlighting potential directions for the future application of BV. We focus on dissecting the underlying mechanisms of BV, discussing its effects on both tumor cells and the tumor microenvironment. Exploring resistance mechanisms in TCL provide valuable insights for optimizing BV-based therapies in the future.
CD30在多种T细胞淋巴瘤（TCL）亚型中过度表达，包括部分外周T细胞淋巴瘤（PTCL）和皮肤T细胞淋巴瘤（CTCL）。靶向CD30阳性细胞的抗体偶联药物维布妥昔单抗（BV）已获批用于治疗复发或难治性系统性间变性大细胞淋巴瘤（sALCL），以及既往接受过全身性治疗的原发性皮肤间变性大细胞淋巴瘤或蕈样肉芽肿患者。然而，许多患者在BV单药治疗后仍出现疾病进展。目前研究重点聚焦于探索BV的有效联合治疗方案。一项III期临床研究表明，对于CD30阳性PTCL患者，BV联合环磷酰胺、多柔比星和泼尼松（CHP）方案优于环磷酰胺、多柔比星、长春新碱和泼尼松（CHOP）方案。该研究促使BV联合CHP方案获准作为CD30阳性PTCL（欧洲为sALCL）的一线治疗方案。本文综述了BV联合疗法令人鼓舞的应用进展，同时列举了正在进行的BV联合治疗研究，以展望其未来应用的潜在方向。我们重点剖析BV的作用机制，探讨其对肿瘤细胞及肿瘤微环境的影响。对TCL耐药机制的探索将为未来优化基于BV的治疗策略提供重要参考。
Antibody–Drug Conjugates Targeting CD30 in T-Cell Lymphomas: Clinical Progression and Mechanism
肿瘤(癌症)患者之家