A Humanized HLA-DR Antibody (HU1D10, Apolizumab) in Combination with G-CSF (Filgrastim) for the Treatment of Non-Hodgkin’s Lymphoma: A Pilot Study.

Apolizumab is a humanized monoclonal antibody against a polymorhic epitope on HLA DRß, which demonstrated evidence for therapeutic activity in follicular lymphoma patients. In preclinical studies, we had previously reported that granulocyte colony-stimulating factor (G-CSF) treatment significantly enhanced lymphoma cell killing by HLA class II antibodies - including Apolizumab. These results suggested a pivotal study of Apolizumab and G-CSF (Filgrastim). In this trial, we treated 6 patients with relapsed or refractory 1D10-positive Non-Hodgkin’s lymphoma with fixed doses of Filgrastim and variable doses of Apolizumab from 0,15 mg/m2 to 1,5 mg/m2. The combination was clinically well tolerated, and all patients received their scheduled drug doses. Two patients experienced grade III/IV hematological toxicity (thrombocytopenia and autoimmune hemolytic anemia, respetively). Another patient developed a pruritic skin rash, which was considered a probably treatment related grade II skin toxicity. On patient with progressive mantle cell lymphoma died from progressive disease at the end of the three month post-treatment period. Interestingly, two patients with follicular lymphoma, who received intensified Apolizumab treatment on a three times weekly schedule, experienced prolonged stabilization of their disease for 12 and for more than 36 month, respectively. In conclusion, this small pilot study suggests that a combination of HLA-class II antibodies and G-CSF is clinically feasable, and that it may induce clinically relevant response in select patients.