Antibody-Drug Conjugates Targeting CD30 in T-Cell Lymphomas: Clinical Progression and Mechanism

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.