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/m2. The treatment was well tolerated, and the maximum tolerated dose was not reached at 64 mg/m2, 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 6 and 3 months, respectively) [corrected], 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.
Hartmann
F
F
Medizinische Klinik I, Universitätskliniken des Saarlandes, Homburg, Germany.
Renner
C
C
Jung
W
W
Deisting
C
C
Juwana
M
M
Eichentopf
B
B
Kloft
M
M
Pfreundschuh
M
M
D000293:Adolescent; D000328:Adult; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006689:Hodgkin Disease / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology*; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000145:classification / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology*; D012074:Remission Induction
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen; D017452:Receptors, IgG