Zanolimumab (HuMax-CD4™), a Fully Human Monoclonal Antibody: Efficacy and Safety in Patients with Relapsed or Treatment-Refractory Non-Cutaneous CD4⁺ T-Cell Lymphoma.

Combination chemotherapy has been the basis of treatment for peripheral T-cell lymphoma (PTCL) for many years, but relapses are frequent, often rapid and usually associated with a poor outcome. New treatment strategies are therefore required. Zanolimumab is a fully human monoclonal cytotoxic IgG1κ antibody, targeting the CD4 molecule on T-cells. The present open-labeled exploratory clinical trial investigated the efficacy and safety of Zanolimumab in 21 patients with biopsy-proven, treatment-refractory or relapsed CD4⁺ PTCL of non-cutaneous type. Zanolimumab was administered by i.v. infusion at a dose of 980 mg once weekly for 12 weeks. Patients (11 male, 10 female, median age 69 years) were enrolled with the following diagnoses: enteropathy-associated T-cell lymphoma (n=1), anaplastic large T-cell lymphoma (ALTL, n=4, 3 ALK^neg subtype, 1 unknown), angioimmunoblastic T-cell lymphoma (n=9) and PTCL-unspecified (n=7). Patients had received a median of 1 previous treatment (range, 1–5) and 3 had undergone high dose chemotherapy with autologous stem cell rescue. The primary endpoint was objective tumor response. Responses were based on CT scan and clinical examination and classified according to the Cheson criteria. Objective tumor response was obtained in 5 out of 21 patients (23.8%; 95% CI: [8.2; 47.2]). Three patients (1 Anaplastic Large T-cell lymphoma and 2 angioimmunoblastic T-cell lymphoma) obtained a partial response of 43 and 51 days duration, respectively, one had not relapsed after 182 days, no further data available. Two patients (PTCL-unspecified and angioimmunoblastic T-cell lymphoma) obtained a complete response (unconfirmed) of 46 days duration and in the latter no relapse after 252 days was observed. 27 serious AEs were reported of which 6 were assessed as related to Zanolimumab treatment. Four infusion related AEs, one transient thrombocytopenia, one febrile neutropenia in a patient that was neutropenic at trial entry. All patients with serious AEs had complete recovery. Two non-serious grade 3 infusion related AEs were reported and one joint pain. In conclusion, zanolimumab was found to be active and well tolerated in heavily pretreated patients with aggressive PTCL. Zanolimumab in combination with CHOP is now being investigated in the setting of previously untreated patients with nodal T-cell lymphoma.