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Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific
antibody
F Hartmann, C Renner, W Jung, C Deisting, M Juwana, B Eichentopf, M Kloft and M Pfreundschuh
Medizinische Klinik I, Universitatskliniken des Saarlandes, Homburg,
Germany.
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 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.
Volume 89,
Issue 6,
pp. 2042-2047,
03/15/1997
Copyright © 1997 by The American Society of Hematology
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