Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody

Fifteen patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc gamma-receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen, respectively, Median counts of NK cells and of all lymphocyte subsets were considerably decreased in the patients before therapy, HRS-3/A9 was administered 4 times every 3 to 4 days, starting with 1 mg/m(2), The treatment was well tolerated, and the maximum tolerated dose was not reached at 64 mg/m(2), the highest dose administered because of the limited amounts of HRS-3/A9 available. Side effects were rare and consisted of fever, pain in involved lymph nodes, and a maculopapulous rash, A total of 9 patients developed human antimouse Ig antibodies, and 4 patients developed an allergic reaction after attempted retreatment. A total of 1 complete and 1 partial remission (lasting 16 and 3 months, respectively), 3 minor responses (1 to 11+ months), and 1 mixed response were achieved. There was no clear-cut dose-side effect or dose-response correlation, Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the murine bispecific antibodies. (C) 1997 by The American Society of Hematology.