Zanolimumab, a Fully Human Monoclonal Antibody: Preliminary Results of an Ongoing Clinical Trial in CD4⁺ Peripheral T-Cell Lymphomas (PTCL).

Zanolimumab (previously referred to as HuMax-CD4) is a fully human monoclonal IgG1k antibody. It is specific for the CD4 antigen expressed on a subset of T cells and has been shown to possess cytotoxic and anti-proliferative effects. We report initial clinical efficacy and safety results following treatment with 980 mg of zanolimumab in 15 patients diagnosed with biopsy-proven, treatment-refractory or relapsed CD4⁺ systemic PTCL. The following PTCL subtypes were included : enteropathy-type T-cell lymphoma (n=1), anaplastic large T-cell lymphoma (ALCL, n=3, 2 alk-negative, 1 alk-status unknown), angioimmunoblastic T-cell lymphoma (AIL, n=8) and PTCL-unspecified (PTCLu, n=3). The primary endpoint of the study was objective tumor response. Responses were based on CT scan and clinical examination and classified according to the Cheson criteria. Out of 15 patients enrolled, 4 responses have been seen; 2 PR (one patient later achieved a CRu) and 2 CRu verified by CT scan. Further, clinical improvements (marked decrease in the size of peripheral lymph nodes) were recorded in 2 additional patients. So far, a total of 21 SAEs has been reported. Of these, 4 were considered related to the study treatment: febrile neutropenia (n=1), thrombocytopenia (n=1), infusion related reaction (n=1) and hyperthermia (38.8° C) with hypotension (n=1). Eight unrelated deaths have been reported so far, all secondary to disease progression. In conclusion, in this heavily pretreated patient population, zanolimumab demonstrated a good tolerability profile and the present results indicate efficacy in the treatment of CD4-positive PTCL.